ORCID Profile
0000-0002-9285-1720
Current Organisation
University of Queensland
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Research Topics
In Research Link Australia (RLA), "Research Topics" refer to ANZSRC FOR and SEO codes. These topics are either sourced from ANZSRC FOR and SEO codes listed in researchers' related grants or generated by a large language model (LLM) based on their publications.
Top 5 Research Topics
ANZSRC Field of Research (FoR)
Biologically active molecules | Natural products and bioactive compounds | Biodiscovery | Environmental biotechnology | Medicinal and biomolecular chemistry | Organic Chemistry | Natural Products Chemistry | Animal Protection (Pests and Pathogens)
ANZSRC Socio-Economic Objective (SEO)
Related Links
Publications
Innovations in Microbial Biodiscovery, Targeting Silent Metabolism and New Chemical Diversity
Publisher: University of Queensland Library
Date: 2013
Viridicatumtoxins: Expanding on a Rare Tetracycline Antibiotic Scaffold
Publisher: American Chemical Society (ACS)
Date: 07-12-2015
Abstract: Viridicatumtoxins, which belong to a rare class of fungal tetracycline-like mycotoxins, were subjected to comprehensive spectroscopic and chemical analysis, leading to reassignment/assignment of absolute configurations and characterization of a remarkably acid-stable antibiotic scaffold. Structure activity relationship studies revealed exceptional growth inhibitory activity against vancomycin-resistant Enterococci (IC50 40 nM), >270-fold more potent than the commercial antibiotic oxytetracycline.
Double adjuvanting strategy for peptide-based vaccines: trimethyl chitosan nanoparticles for lipopeptide delivery
Publisher: Future Medicine Ltd
Date: 12-2016
Abstract: Aim: To develop novel polymer-based nanoscale delivery system for lipopeptide-based vaccine against group A Streptococcus (GAS). Materials & methods: Four types of lipopeptide antigen-loaded polymeric nanoparticles (NP) were prepared. NP were accessed for their capacity to be taken up by dendritic cells effect on dendritic cell maturation ability to induce mucosal and systemic immunity and capability to induce antibody responses that opsonize GAS bacteria. Results & discussion: The combination of adjuvanting properties of lipopeptides and dextran/trimethyl chitosan-based NP had a synergistic effect on humoral immunity, and the produced antibodies showed high opsonic activity against clinical GAS isolates. Conclusion: Biocompatible NP-bearing trimethyl chitosan and dextran are efficient as mucosal adjuvants for the intranasal delivery of lipopeptide-based vaccines.
Noonindoles G–L: Indole Diterpene Glycosides from the Australian Marine-Derived Fungus Aspergillus noonimiae CMB-M0339
Publisher: American Chemical Society (ACS)
Date: 20-01-2023
Trivirensols: Selectively Bacteriostatic Sesquiterpene Trimers from the Australian Termite Nest-Derived Fungus Trichoderma virens CMB-TN16
Publisher: American Chemical Society (ACS)
Date: 18-10-2019
DOI: 10.1021/ACS.JNATPROD.9B00760
Abstract: The termite nest-derived fungus
Polycyclic C-deoxyaminoglycoside-polyketides from an Australian Pasture Plant Derived Streptomyces sp.
Publisher: American Chemical Society (ACS)
Date: 15-10-2021
DOI: 10.1021/ACS.ORGLETT.1C02954
Abstract: The Australian plant pasture-derived
Development of Polyelectrolyte Complexes for the Delivery of Peptide-Based Subunit Vaccines against Group A Streptococcus.
Publisher: MDPI AG
Date: 26-04-2020
DOI: 10.3390/NANO10050823
Abstract: Peptide subunit vaccines hold great potential compared to traditional vaccines. However, peptides alone are poorly immunogenic. Therefore, it is of great importance that a vaccine delivery platform and/or adjuvant that enhances the immunogenicity of peptide antigens is developed. Here, we report the development of two different systems for the delivery of lipopeptide subunit vaccine (LCP-1) against group A streptococcus: polymer-coated liposomes and polyelectrolyte complexes (PECs). First, LCP-1-loaded and alginate/trimethyl chitosan (TMC)-coated liposomes (Lip-1) and LCP-1/alginate/TMC PECs (PEC-1) were examined for their ability to trigger required immune responses in outbred Swiss mice PEC-1 induced stronger humoral immune responses than Lip-1. To further assess the adjuvanting effect of anionic polymers in PECs, a series of PECs (PEC-1 to PEC-5) were prepared by mixing LCP-1 with different anionic polymers, namely alginate, chondroitin sulfate, dextran, hyaluronic acid, and heparin, then coated with TMC. All produced PECs had similar particle sizes (around 200 nm) and surface charges (around + 30 mV). Notably, PEC-5, which contained heparin, induced higher antigen-specific systemic IgG and mucosal IgA titers than all other PECs. PEC systems, especially when containing heparin and TMC, could function as a promising platform for peptide-based subunit vaccine delivery for intranasal administration.
Inter-Kingdom beach warfare: Microbial chemical communication activates natural chemical defences
Publisher: Springer Science and Business Media LLC
Date: 16-08-2018
Ikirydinium A: a new indole alkaloid from the seeds of Hunteria umbellata (K. Schum)
Publisher: Elsevier BV
Date: 12-2011
Chrysosporazines F–M: P-Glycoprotein Inhibitory Phenylpropanoid Piperazines from an Australian Marine Fish Derived Fungus, Chrysosporium sp. CMB-F294
Publisher: American Chemical Society (ACS)
Date: 24-01-2020
DOI: 10.1021/ACS.JNATPROD.9B01181
Abstract: Chemical analysis of the fungus
Chemical Diversity from a Chinese Marine Red Alga, Symphyocladia latiuscula
Publisher: MDPI AG
Date: 12-2017
DOI: 10.3390/MD15120374
Chrysosporazines A–E: P-Glycoprotein Inhibitory Piperazines from an Australian Marine Fish Gastrointestinal Tract-Derived Fungus, Chrysosporium sp. CMB-F214
Publisher: American Chemical Society (ACS)
Date: 23-09-2019
DOI: 10.1021/ACS.ORGLETT.9B03094
Abstract: Chemical analysis of
Glenthmycins A–M: Macrocyclic Spirotetronate Polyketide Antibacterials from the Australian Pasture Plant-Derived Streptomyces sp. CMB-PB041
Publisher: American Chemical Society (ACS)
Date: 31-05-2022
DOI: 10.1021/ACS.JNATPROD.2C00444
Abstract: Chemical investigation of Australian pasture plant-derived
Microbioreactor techniques for the production and spectroscopic characterization of microbial peptides
Publisher: Springer US
Date: 27-12-2019
DOI: 10.1007/978-1-0716-0227-0_21
Abstract: We have demonstrated that the simple and low-cost microbioreactor can speed up the bioprocessing techniques by using small amount of reagents and very few seed cultures to give results comparable with those obtained from the shake flask. The microbioreactor has the potential of replacing the normal conventional-scale process and offers a high-throughput efficient and analytical technique in addressing some of the challenges encountered in bioprocessing starting that includes bacterial growth and secondary metabolites production targeting the discovery of new antibacterial peptides. In our case studies, we proved that microbes were capable of growing in the microbioreactor and the production of microbial secondary metabolites (i.e., peptides) was detectable in HPLC-DAD-MS. We used QTOF-MS/MS to detect the production of peptides in the microbial culture. The purified peptides were characterized using 1D and 2D NMR, QTOF-MS/MS, and Marfey's analysis.
Roseopurpurins: Chemical Diversity Enhanced by Convergent Biosynthesis and Forward and Reverse Michael Additions
Publisher: American Chemical Society (ACS)
Date: 18-08-2016
DOI: 10.1021/ACS.ORGLETT.6B02099
Abstract: Cultures of the estuarine fungus Penicillium roseopurpureum (CMB-MF038) yielded a erse array of polyketides, many of which were related via a highly convergent biosynthetic pathway. In addition to revising and assigning structures, and documenting chemical and biological properties, pro-drug cytotoxic properties were attributed to roseopurpurins H (10) and I (11) on the basis of in situ reverse Michael addition to a cytotoxic Michael acceptor (12).
Atropselective syntheses of (−) and (+) rugulotrosin A utilizing point-to-axial chirality transfer
Publisher: Springer Science and Business Media LLC
Date: 02-02-2015
DOI: 10.1038/NCHEM.2173
Development of Multilayer Nanoparticles for the Delivery of Peptide-Based Subunit Vaccine against Group A Streptococcus
Publisher: MDPI AG
Date: 10-10-2022
DOI: 10.3390/PHARMACEUTICS14102151
Abstract: Peptide-based subunit vaccines include only minimal antigenic determinants, and, therefore, are less likely to induce allergic immune responses and adverse effects compared to traditional vaccines. However, peptides are weakly immunogenic and susceptible to enzymatic degradation when administered on their own. Hence, we designed polyelectrolyte complex (PEC)-based delivery systems to protect peptide antigens from degradation and improve immunogenicity. Lipopeptide (LCP-1) bearing J8 B-cell epitope derived from Group A Streptococcus (GAS) M-protein was selected as the model peptide antigen. In the pilot study, LCP-1 incorporated in alginate/cross-linked polyarginine-J8-based PEC induced high J8-specific IgG antibody titres. The PEC system was then further modified to improve its immune stimulating capability. Of the formulations tested, PEC-4, bearing LCP-1, alginate and cross-linked polylysine, induced the highest antibody titres in BALB/c mice following subcutaneous immunisation. The antibodies produced were more opsonic than those induced by mice immunised with other PECs, and as opsonic as those induced by antigen adjuvanted with powerful complete Freund’s adjuvant.
Poly(hydrophobic amino acid) Conjugates for the Delivery of Multiepitope Vaccine against Group A Streptococcus
Publisher: American Chemical Society (ACS)
Date: 11-08-2021
DOI: 10.1021/ACS.BIOCONJCHEM.1C00333
Abstract: Peptide-based vaccines are composed of small, defined, antigenic peptide epitopes. They are designed to induce well-controlled immune responses. Multiple epitopes are often employed in these vaccines to cover strain variability of a pathogen. However, peptide epitopes cannot stimulate adequate immune responses on their own and require an adjuvant (immune stimulant) and/or delivery system. Here, we designed and synthesized a multiepitope vaccine candidate against Group A Streptococcus (GAS) composed of several B-cell epitopes (J8, PL1, and 88/30) derived from GAS M-protein, universal PADRE T-helper cell epitope, and a polyleucine self-adjuvanting unit. The vaccine components were conjugated together (using mercapto-maleimide and azide-alkyne Huisgen cycloaddition reactions) or delivered as a mixture. The conjugated multiepitope vaccine candidate self-assembled into small nanoparticles and chain-like aggregated nanoparticles (CLANs) that were able to induce the production of J8-, PL1-, and 88/30-specific antibodies in mice. The multiepitope conjugate and the physical mixture of conjugates bearing the in idual epitopes produced similar nanoparticles and induced comparable immune responses. Hence, simple physical mixing can replace complex chemical conjugation to produce multiepitope nanoparticles with equivalent morphology and immunological efficacy. This greatly simplifies vaccine production.
N-Amino-l-Proline Methyl Ester from an Australian Fish Gut-Derived Fungus: Challenging the Distinction between Natural Product and Artifact
Publisher: MDPI AG
Date: 12-03-2021
DOI: 10.3390/MD19030151
Abstract: Further investigation into a fish gut-derived fungus Evlachovaea sp. CMB-F563, previously reported to produce the unprecedented Schiff base prolinimines A–B (1–2), revealed a new cryptic natural product, N-amino-l-proline methyl ester (5)—only the second reported natural occurrence of an N-amino-proline, and the first from a microbial source. To enable these investigations, we developed a highly sensitive analytical derivitization methodology, using 2,4-dinitrobenzaldehyde (2,4-DNB) to cause a rapid in situ transformation of 5 to the Schiff base 9, with the latter more readily detectable by UHPLC-DAD (400 nm) and HPLC-MS analyses. Moreover, we demonstrate that during cultivation 5 is retained in fungal mycelia, and it is only when solvent extraction disrupts mycelia that 5 is released to come in contact with the furans 7–8 (which are themselves produced by thermal transformation of carbohydrates during media autoclaving prior to fungal inoculation). Significantly, on contact, 5 undergoes a spontaneous condensation with 7–8 to yield the Schiff base prolinimines 1–2, respectively. Observations made during this study prompted us to reflect on what it is to be a natural product (i.e., 5), versus an artifact (i.e., 1–2), versus a media component (i.e., 7–8).
Solvolysis artifacts: Leucettazoles as cryptic macrocyclic alkaloid dimers from a Southern Australian marine sponge, Leucetta sp.
Publisher: MDPI AG
Date: 09-02-2019
DOI: 10.3390/MD17020106
Abstract: Keywords: ethanolysis solvolysis artifact leucettazoles leucettazines macrocyclic alkaloids Leucetta Australian sponge GNPS.
A search for kinase inhibitors and antibacterial agents: bromopyrrolo-2-aminoimidazoles from a deep-water Great Australian Bight sponge, Axinella sp.
Publisher: Elsevier BV
Date: 07-2012
Talarophenol sulfate and talarophilones from the Australian mud dauber wasp-associated fungus, Talaromyces sp. CMB-W045
Publisher: Elsevier BV
Date: 10-2019
Lipid core peptide/poly(lactic-co-glycolic acid) as a highly potent intranasal vaccine delivery system against Group A streptococcus
Publisher: Elsevier BV
Date: 11-2016
DOI: 10.1016/J.IJPHARM.2016.09.057
Abstract: Rheumatic heart disease represents a leading cause of mortality caused by Group A Streptococcus (GAS) infections transmitted through the respiratory route. Although GAS infections can be treated with antibiotics these are often inadequate. An efficacious GAS vaccine holds more promise, with intranasal vaccination especially attractive, as it mimics the natural route of infections and should be able to induce mucosal IgA and systemic IgG immunity. Nanoparticles were prepared by either encapsulating or coating lipopeptide-based vaccine candidate (LCP-1) on the surface of poly(lactic-co-glycolic acid) (PLGA). In vitro study showed that encapsulation of LCP-1 vaccine into nanoparticles improved uptake and maturations of antigen-presenting cells. The immunogenicity of lipopeptide incorporated PLGA-based nanoparticles was compared with peptides co-administered with mucosal adjuvant cholera toxin B in mice upon intranasal administration. Higher levels of J14-specific salivary mucosal IgA and systemic antibody IgG titres were observed for groups immunized with encapsulated LCP-1 compared to LCP-1 coated nanoparticles or free LCP-1. Systemic antibodies obtained from LCP-1 encapsulated PLGA NPs inhibited the growth of bacteria in six different GAS strains. Our results show that PLGA-based lipopeptide delivery is a promising approach for rational design of a simple, effective and patient friendly intranasal GAS vaccine resulting in mucosal IgA response.
Talarolides Revisited: Cyclic Heptapeptides from an Australian Marine Tunicate-Associated Fungus, Talaromyces sp. CMB-TU011
Publisher: MDPI AG
Date: 11-09-2023
DOI: 10.3390/MD21090487
A dual-adjuvanting strategy for peptide-based subunit vaccines against group A Streptococcus: Lipidation and polyelectrolyte complexes
Publisher: Elsevier BV
Date: 12-2020
Wollamides: Antimycobacterial cyclic hexapeptides from an australian soil Streptomyces
Publisher: American Chemical Society (ACS)
Date: 17-09-2014
DOI: 10.1021/OL502472C
Abstract: A soil Streptomyces nov. sp. (MST-115088) isolated from semiarid terrain near Wollogorang Station, Queensland, returned two known and two new ex les of a rare class of cyclic hexapeptide, desotamides A and B (1 and 2) and E and F (3 and 4), respectively, together with two new d-Orn homologues, wollamides A and B (5 and 6). Structures were assigned by detailed spectroscopic and C3 Marfey's analysis. The desotamides/wollamides exhibit growth inhibitory activity against Gram-positive bacteria (IC50 0.6-7 μM) and are noncytotoxic to mammalian cells (IC50 >30 μM). The wollamides exhibit antimycobacterial activity (IC50 2.8 and 3.1 μM), including reduction in the intracellular mycobacterial survival in murine bone marrow-derived macrophages.
Aranciamycins I and J, Antimycobacterial Anthracyclines from an Australian Marine-Derived Streptomyces sp.
Publisher: American Chemical Society (ACS)
Date: 19-03-2015
DOI: 10.1021/ACS.JNATPROD.5B00095
Abstract: Chemical analysis of an Australian marine-derived Streptomyces sp. (CMB-M0150) yielded two new anthracycline antibiotics, aranciamycins I (1) and J (2), as well as the previously reported aranciamycin A (3) and aranciamycin (4). The aranciamycins 1-4, identified by detailed spectroscopic analysis, were noncytotoxic when tested against selected Gram-negative bacteria and fungi (IC50 >30 μM) and exhibited moderate and selective cytotoxicity against Gram-positive bacteria (IC50 >1.1 μM) and a panel of human cancer cell lines (IC50 > 7.5 μM). Significantly, 1-4 were cytotoxic (IC50 0.7-1.7 μM) against the Mycobacterium tuberculosis surrogate M. bovis bacille Calmette-Guérin.
Heterofibrins: inhibitors of lipid droplet formation from a deep-water southern Australian marine sponge, Spongia (Heterofibria) sp.
Publisher: Royal Society of Chemistry (RSC)
Date: 2010
DOI: 10.1039/C003840G
Abstract: A bioassay-guided search for inhibitors of lipid droplet formation in a deep-water southern Australian marine sponge, Spongia (Heterofibria) sp., yielded six new compounds, fatty acids heterofibrins A1 (1) and B1 (4), along with related monolactyl and dilactyl esters, heterofibrins A2 (2), B2 (5), A3 (3) and B3 (6). Heterofibrin structures were assigned on the basis of detailed spectroscopic analysis, with comparison to chiral synthetic model compounds. All heterofibrins possess a diyne-ene moiety, while the monolactyl and dilactyl moiety featured in selected heterofibrins is unprecedented in the natural products literature. SAR by co-metabolite studies on the heterofibrins confirmed them to be non-cytotoxic, with the carboxylic acids 1 and 4 inhibiting lipid droplet formation in A431 fibroblast cell lines. Such inhibitors have potential application in the management of obesity, diabetes and atherosclerosis
Polyglutamic acid-trimethyl chitosan-based intranasal peptide nano-vaccine induces potent immune responses against group A streptococcus
Publisher: Elsevier BV
Date: 10-2018
DOI: 10.1016/J.ACTBIO.2018.09.037
Abstract: Peptide-based vaccines have the potential to overcome the limitations of classical vaccines however, their use is h ered by a lack of carriers and adjuvants suitable for human use. In this study, an efficient self-adjuvanting peptide vaccine delivery system was developed based on the ionic interactions between cationic trimethyl chitosan (TMC) and a peptide antigen coupled with synthetically defined anionic α-poly-(l-glutamic acid) (PGA). The antigen, possessing a conserved B-cell epitope derived from the group A streptococcus (GAS) pathogen and a universal T-helper epitope, was conjugated to PGA using cycloaddition reaction. The produced anionic conjugate formed nanoparticles (NP-1) through interaction with cationic TMC. These NP-1 induced higher systemic and mucosal antibody titers compared to antigen adjuvanted with standard mucosal adjuvant cholera toxin B subunit or antigen mixed with TMC. The produced serum antibodies were also opsonic against clinically isolated GAS strains. Further, a reduction in bacterial burden was observed in nasal secretions, pharyngeal surface and nasopharyngeal-associated lymphoid tissue of mice immunized with NP-1 in GAS challenge studies. Thus, conjugation of defined-length anionic polymer to peptide antigen as a means of formulating ionic interaction-based nanoparticles with cationic polymer is a promising strategy for peptide antigen delivery. STATEMENT OF SIGNIFICANCE: A self-adjuvanting delivery system is required for peptide vaccines to enhance antigen delivery to immune cells and generate systemic and mucosal immunity. Herein, we developed a novel self-adjuvanting nanoparticulate delivery system for peptide antigens by combining polymer-conjugation and complexation strategies. We conjugated peptide antigen with anionic α-poly-(l-glutamic acid) that in turn, formed nanoparticles with cationic trimethyl chitosan by ionic interactions, without using external crosslinker. On intranasal administration to mice, these nanoparticles induced systemic and mucosal immunity, at low dose. Additionally, nanoparticles provided protection to vaccinated mice against group A streptococcus infection. Thus, this concept should be particularly useful in developing nanoparticles for the delivery of peptide antigens.
Polyethylenimine: An Intranasal Adjuvant for Liposomal Peptide-Based Subunit Vaccine against Group A Streptococcus
Publisher: American Chemical Society (ACS)
Date: 07-08-2020
Fungal Biotransformation of Tetracycline Antibiotics
Publisher: American Chemical Society (ACS)
Date: 25-07-2016
Abstract: The commercial antibiotics tetracycline (3), minocycline (4), chlortetracycline (5), oxytetracycline (6), and doxycycline (7) were biotransformed by a marine-derived fungus Paecilomyces sp. to yield seco-cyclines A-H (9-14, 18 and 19) and hemi-cyclines A-E (20-24). Structures were assigned by detailed spectroscopic analysis, and in the case of 10 X-ray crystallography. Parallel mechanisms account for substrate-product specificity, where 3-5 yield seco-cyclines and 6 and 7 yield hemi-cyclines. The susceptibility of 3-7 to fungal biotransformation is indicative of an unexpected potential for tetracycline "degradation" (i.e., antibiotic resistance) in fungal genomes. Significantly, the fungal-derived tetracycline-like viridicatumtoxins are resistant to fungal biotransformation, providing chemical insights that could inform the development of new tetracycline antibiotics resistant to enzymatic degradation.
Exploring Natural Product Artifacts: The Polyketide Enterocin Warms to a Ballet of Isomers
Publisher: American Chemical Society (ACS)
Date: 08-06-2020
Levoglucosenone and Its Pseudoenantiomer iso-Levoglucosenone as Scaffolds for Drug Discovery and Development
Publisher: American Chemical Society (ACS)
Date: 08-06-2020
Scopularides Revisited: Molecular Networking Guided Exploration of Lipodepsipeptides in Australian Marine Fish Gastrointestinal Tract-Derived Fungi
Publisher: MDPI AG
Date: 16-08-2019
DOI: 10.3390/MD17080475
Abstract: Chemical analysis of a cultivation of an Australian Mugil mullet gastrointestinal tract (GIT) derived fungus, Scopulariopsis sp. CMB-F458, yielded the known lipodepsipeptides scopularides A (1) and B (2). A comparative global natural product social (GNPS) molecular networking analysis of ×63 co-isolated fungi, detected two additional fungi producing new scopularides, with Beauveria sp. CMB-F585 yielding scopularides C–G (3–7) and Scopulariopsis sp. CMB-F115 yielding scopularide H (8). Structures inclusive of absolute configurations were assigned by detailed spectroscopic and C3 Marfey’s analysis, together with X-ray analyses of 3 and 8, and biosynthetic considerations. Scopularides A–H (1–8) did not exhibit significant growth inhibitory activity against a selection of Gram positive (+ve) and negative (−ve) bacteria, a fungus, or a panel of three human carcinoma cell lines.
Glenthenamines A–F: Enamine Pyranonaphthoquinones from the Australian Pasture Plant Derived Streptomyces sp. CMB-PB042
Publisher: American Chemical Society (ACS)
Date: 24-01-2022
DOI: 10.1021/ACS.JNATPROD.1C00821
Abstract: Chemical investigations into solid phase cultivations of an Australian sheep station pasture plant derived
Neochrysosporazines: Precursor-Directed Biosynthesis Defines a Marine-Derived Fungal Natural Product P-Glycoprotein Inhibitory Pharmacophore
Publisher: American Chemical Society (ACS)
Date: 22-01-2022
DOI: 10.1021/ACS.JMEDCHEM.1C01989
Abstract: Upregulation of ATP binding cassette (ABC) transporter efflux pumps (
A search for BACE inhibitors reveals new biosynthetically related pyrrolidones, furanones and pyrroles from a southern Australian marine sponge, Ianthella sp.
Publisher: Royal Society of Chemistry (RSC)
Date: 2012
DOI: 10.1039/C2OB06747A
Abstract: Fractionation of a southern Australian marine sponge, Ianthella sp., yielded sixteen metabolites including a new class of pyrrolidone, ianthellidones A-F (1-6), a new class of furanone, ianthellidones G-H (7-8), new and known lamellarins, lamellarins O1 (9), O2 (10), O (11) and Q (12), plus the known 4-hydroxybenzaldehyde (13), 4-hydroxybenzoic acid (14), 4-methoxybenzoic acid (15) and ethyl 4-hydroxybenzoate (16). Structures for all Ianthella metabolites were determined by detailed spectroscopic analysis, supported by a plausible biosynthetic relationship. The ianthellidones were non-cytotoxic towards two human colon cancer cell lines (SW620 and SW620 Ad300), as well as Gram +ve and Gram -ve bacteria, and a fungus. Ianthellidone F (6) and lamellarins O2 (10) and O (11) displayed modest BACE inhibitory properties (IC(50) > 10 μM), while lamellarin O1 (9) was more potent (IC(50) 22 μM), was an inhibitor of the multi-drug resistance efflux pump P-glycoprotein, and displayed selective growth inhibitory activity against the Gram +ve bacterium Bacillus subtilis (ATCC 6633) (IC(50) 2.5 μM).
Prolinimines: N-Amino-l -Pro-methyl Ester (Hydrazine) Schiff Bases from a Fish Gastrointestinal Tract-Derived Fungus, Trichoderma sp. CMB-F563
Publisher: American Chemical Society (ACS)
Date: 09-01-2018
DOI: 10.1021/ACS.ORGLETT.7B03666
Abstract: A rice cultivation of a fish gastrointestinal tract-derived fungus, Trichoderma sp. CMB-F563, yielded natural products incorporating a rare hydrazine moiety, embedded within a Schiff base. Structures inclusive of absolute configurations were assigned to prolinimines A-D (1-4) on the basis of detailed spectroscopic and C
Cell-Penetrating Peptides-Based Liposomal Delivery System Enhanced Immunogenicity of Peptide-Based Vaccine against Group A Streptococcus
Publisher: MDPI AG
Date: 12-05-2021
Abstract: Peptide-based vaccine development represents a highly promising strategy for preventing Group A Streptococcus (GAS) infection. However, these vaccines need to be administered with the help of a delivery system and/or immune adjuvant. Cell-penetrating peptides (CPPs) have been used as a powerful tool for delivering various therapeutic agents, including peptides, as they can overcome the permeability barrier of cell membranes. Here, we used CPPs to deliver our lead lipopeptide-based vaccine (LCP-1). CPPs were anchored through a spacer to LCP-1-bearing multilamellar and unilamellar liposomes and administered to Swiss outbred mice. Tat47–57 conjugated to two palmitic acids via a (Gly)6 spacer (to form a liposome-anchoring moiety) was the most efficient system for triggering immune responses when combined with multilamellar liposomes bearing LCP-1. The immunostimulatory potential of a variety of other CPPs was examined following intranasal administration in mice. Among them, LCP-1/liposomes/Tat47–57 and LCP-1/liposomes/KALA induced the highest antibody titers. The antibodies produced showed high opsonic activity against clinically isolated GAS strains D3840 and GC2 203. The use of the CPP-liposome delivery system is a promising strategy for liposome-based GAS vaccine development.
Trichodermides A–E: New Peptaibols Isolated from the Australian Termite Nest-Derived Fungus Trichoderma virens CMB-TN16
Publisher: American Chemical Society (ACS)
Date: 12-03-2018
DOI: 10.1021/ACS.JNATPROD.7B01072
Abstract: Chemical analysis of a fermentation of the Australian termite nest-derived fungus Trichoderma virens CMB-TN16 yielded five new acyclic nonapeptides, trichodermides A-E (1-5). Amino acid residues, configurations, and sequences were determined by a combination of spectroscopic (NMR and MS-MS) and chemical (C
Linear and branched polyacrylates as a delivery platform for peptide-based vaccines
Publisher: Future Science Ltd
Date: 09-2016
Abstract: Aim: Peptide-based vaccines are designed to carry the minimum required antigen to trigger the desired immune responses however, they are usually poorly immunogenic and require appropriate delivery system. Results: Peptides, B-cell epitope (J14) derived from group A streptococcus M-protein and universal T-helper (PADRE) epitope, were conjugated to a variety of linear and branched polyacrylates. All produced conjugates formed submicron-sized particles and induced a high level of IgG titres in mice after subcutaneous immunization. These polymer–peptide conjugates demonstrated high opsonization capacity against group A streptococcus clinical isolates. Conclusion: We have successfully demonstrated that submicron-sized polymer–peptide conjugates were capable of inducing strong humoral immune responses after single immunization.
Activity Relationship of Poly(ethylenimine)-Based Liposomes as Group A Streptococcus Vaccine Delivery Systems
Publisher: American Chemical Society (ACS)
Date: 25-07-2023
Methods in Microbial Biodiscovery
Publisher: MDPI AG
Date: 03-09-2021
DOI: 10.3390/MD19090503
Abstract: This review presents an account of the microbial biodiscovery methodology developed and applied in our laboratory at The University of Queensland, Institute for Molecular Bioscience, with ex les drawn from our experiences studying natural products produced by Australian marine-derived (and terrestrial) fungi and bacteria.
Oxandrastins: Antibacterial Meroterpenes from an Australian Mud Dauber Wasp Nest-Associated Fungus, Penicillium sp. CMB-MD14
Publisher: MDPI AG
Date: 25-11-2021
DOI: 10.3390/MOLECULES26237144
Abstract: The ethyl acetate extract of an ISP-2 agar cultivation of the wasp nest-associated fungus Penicillium sp. CMB-MD14 exhibited promising antibacterial activity against vancomycin-resistant enterococci (VRE), with a bioassay guided chemical investigation yielding the new meroterpene, oxandrastin A (1), the first andrastin-like metabolite with an extra oxygenation at C-2. A culture media optimisation strategy informed a scaled-up rice cultivation that yielded 1, together with three new oxandrastins B–D (2–4), two known andrastins C (5) and F (6), and a new meroterpene of the austalide family, isoaustalide F (7). Structures of 1–7 were assigned based on detailed spectroscopic analysis and chemical interconversion. A GNPS molecular networking analysis of the rice cultivation extract detected the known austalides B (8), H (9), and H acid (10), tentatively identified based on molecular formulae and co-clustering with 7. That the anti-VRE properties of the CMB-MD14 extract were exclusively attributed to 1 (IC50 6.0 µM, MIC99 13.9 µM), highlights the importance of the 2-OAc and 3-OAc moieties to the oxandrastin anti-VRE pharmacophore.
Lincolnenins A-D: Isomeric Bactericidal Bianthracenes from Streptomyces lincolnensis
Publisher: American Chemical Society (ACS)
Date: 15-12-2021
Noonindoles A–F: Rare Indole Diterpene Amino Acid Conjugates from a Marine-Derived Fungus, Aspergillus noonimiae CMB-M0339
Publisher: MDPI AG
Date: 07-11-2022
DOI: 10.3390/MD20110698
Abstract: Analytical scale chemical/cultivation profiling prioritized the Australian marine-derived fungus Aspergillus noonimiae CMB-M0339. Subsequent investigation permitted isolation of noonindoles A–F (5–10) and detection of eight minor analogues (i–viii) as new ex les of a rare class of indole diterpene (IDT) amino acid conjugate, indicative of an acyl amino acid transferase capable of incorporating a erse range of amino acid residues. Structures for 5–10 were assigned by detailed spectroscopic and X-ray crystallographic analysis. The metabolites 5–14 exhibited no antibacterial properties against G-ve and G+ve bacteria or the fungus Candida albicans, with the exception of 5 which exhibited moderate antifungal activity.
The Development of Surface-Modified Liposomes as an Intranasal Delivery System for Group A Streptococcus Vaccines
Publisher: MDPI AG
Date: 30-01-2023
Abstract: Intranasal vaccine administration can overcome the disadvantages of injectable vaccines and present greater efficiency for mass immunization. However, the development of intranasal vaccines is challenged by poor mucosal immunogenicity of antigens and the limited availability of mucosal adjuvants. Here, we examined a number of self-adjuvanting liposomal systems for intranasal delivery of lipopeptide vaccine against group A Streptococcus (GAS). Among them, two liposome formulations bearing lipidated cell-penetrating peptide KALA and a new lipidated chitosan derivative (oleoyl-quaternized chitosan, OTMC) stimulated high systemic antibody titers in outbred mice. The antibodies were fully functional and were able to kill GAS bacteria. Importantly, OTMC was far more effective at stimulating antibody production than the classical immune-stimulating trimethyl chitosan formulation. In a simple physical mixture, OTMC also enhanced the immune responses of the tested vaccine, without the need for a liposome delivery system. The adjuvanting capacity of OTMC was further confirmed by its ability to stimulate cytokine production by dendritic cells. Thus, we discovered a new immune stimulant with promising properties for mucosal vaccine development.
Isolation and synthesis of N-acyladenine and adenosine alkaloids from a southern Australian marine sponge, Phoriospongia sp.
Publisher: Elsevier BV
Date: 10-2014
Genomic and Metabolomic Analysis of Antarctic Bacteria Revealed Culture and Elicitation Conditions for the Production of Antimicrobial Compounds
Publisher: MDPI AG
Date: 27-04-2020
DOI: 10.3390/BIOM10050673
Abstract: Concern about finding new antibiotics against drug-resistant pathogens is increasing every year. Antarctic bacteria have been proposed as an unexplored source of bioactive metabolites however, most biosynthetic gene clusters (BGCs) producing secondary metabolites remain silent under common culture conditions. Our work aimed to characterize elicitation conditions for the production of antibacterial secondary metabolites from 34 Antarctic bacterial strains based on MS/MS metabolomics and genome mining approaches. Bacterial strains were cultivated under different nutrient and elicitation conditions, including the addition of lipopolysaccharide (LPS), sodium nitroprusside (SNP), and coculture. Metabolomes were obtained by HPLC-QTOF-MS/MS and analyzed through molecular networking. Antibacterial activity was determined, and seven strains were selected for genome sequencing and analysis. Biosynthesis pathways were activated by all the elicitation treatments, which varies among strains and dependents of culture media. Increased antibacterial activity was observed for a few strains and addition of LPS was related with inhibition of Gram-negative pathogens. Antibiotic BGCs were found for all selected strains and the expressions of putative actinomycin, carotenoids, and bacillibactin were characterized by comparison of genomic and metabolomic data. This work established the use of promising new elicitors for bioprospection of Antarctic bacteria and highlights the importance of new “-omics” comparative approaches for drug discovery.
Chrysosporazines Revisited: Regioisomeric Phenylpropanoid Piperazine P-Glycoprotein Inhibitors from Australian Marine Fish-Derived Fungi
Publisher: MDPI AG
Date: 16-05-2022
DOI: 10.3390/MOLECULES27103172
Abstract: A library of fungi previously recovered from the gastrointestinal tract (GIT) of several fresh, commercially sourced Australian mullet fish was re-profiled for production of a rare class of phenylpropanoid piperazine alkaloids (chrysosporazines) using an integrated platform of (i) miniaturized 24-well plate cultivation profiling (MATRIX), (ii) UPLC-DAD and UPLC-QTOF-MS/MS (GNPS) chemical profiling, and (iii) precursor directed biosynthesis to manipulate in situ biosynthetic performance and outputs to detect two new fungal producers of chrysosporazines. Chemical analysis of an optimized PDA solid phase cultivation of Aspergillus sp. CMB-F661 yielded the new regioisomeric chrysosporazine T (1) and U (2), while precursor directed cultivation lified production and yielded the very minor new natural products azachrysosporazine T1 (3) and U1 (4), and the new unnatural analogues neochrysosporazine R (5) and S (6). Likewise, chemical analysis of an optimized M1 solid phase cultivation of Spiromastix sp. CMB-F455 lead to the GNPS detection of multiple chrysosporazines and brasiliamides, and the isolation and structure elucidation of chrysosporazine D (7) and brasiliamide A (8). Access to new chrysosporazine regioisomers facilitated structure activity relationship investigations to better define the chrysosporazine P-glycoprotein (P-gp) inhibitory pharmacophore, which is exceptionally potent at reversing doxorubrin resistance in P-gp over expressing colon carcinoma cells (SW600 Ad300).
Bromocatechol conjugates from a Chinese marine red alga, Symphyocladia latiuscula
Publisher: Elsevier BV
Date: 02-2019
DOI: 10.1016/J.PHYTOCHEM.2018.10.026
Abstract: This study describes an investigation into polybromocatechol conjugates isolated from a marine red alga, Symphyocladia latiuscula (Harvey) Yamada, collected from coastal waters off Qingdao, China. We report on the isolation and characterisation of eight undescribed aconitic acid conjugates, symphyocladins R-X, including a likely solvolysis artifact of symphyocladin S, and an undescribed furanoyl conjugate, symphyocladin Y. Structure elucidation was achieved by detailed spectroscopic analysis. A plausible biosynthetic pathway linking all these co-metabolites through a cascade of quinone methide additions is proposed.
Heronapyrrole D: A case of co-inspiration of natural product biosynthesis, total synthesis and biodiscovery
Publisher: Beilstein Institut
Date: 26-05-2014
DOI: 10.3762/BJOC.10.121
Abstract: The heronapyrroles A–C have first been isolated from a marine-derived Streptomyces sp. (CMB-0423) in 2010. Structurally, these natural products feature an unusual nitropyrrole system to which a partially oxidized farnesyl chain is attached. The varying degree of oxidation of the sesquiterpenyl subunit in heronapyrroles A–C provoked the hypothesis that there might exist other hitherto unidentified metabolites. On biosynthetic grounds a mono-tetrahydrofuran-diol named heronapyrrole D appeared a possible candidate. We here describe a short asymmetric synthesis of heronapyrrole D, its detection in cultivations of CMB-0423 and finally the evaluation of its antibacterial activity. We thus demonstrate that biosynthetic considerations and the joint effort of synthetic and natural product chemists can result in the identification of new members of a rare class of natural products.
Self-assembling lipopeptides with a potent activity against Gram-positive bacteria, including multidrug resistant strains
Publisher: Future Medicine Ltd
Date: 11-2015
DOI: 10.2217/NNM.15.137
Abstract: Aim: To explore the potential of de novo designed cyclic lipopeptides and its linear counterparts as antibacterial agents. Materials & methods: The lipopeptides were synthesized via solid-phase peptide synthesis and the cyclization was achieved by using succinic acid linker. The antimicrobial activities of the lipopeptides were evaluated in vitro against a variety selection of Gram-negative and Gram-positive bacteria including clinical isolates of multidrug-resistant strains. Results: The synthesized lipopeptides were able to self-assemble into nanoparticles in an aqueous environment, with three exhibiting potent antibacterial activity against Gram-positive bacteria, including clinically relevant multidrug-resistant bacteria. Conclusion: The lead compounds have the potential to be developed as new antibacterials that are effective against Gram-positive bacteria, including multidrug-resistant isolates.
Heronamycin A: a new benzothiazine ansamycin from an Australian marine-derived Streptomyces sp.
Publisher: Elsevier BV
Date: 02-2012
Shornephine A: Structure, Chemical Stability, and P-Glycoprotein Inhibitory Properties of a Rare Diketomorpholine from an Australian Marine-Derived Aspergillus sp.
Publisher: American Chemical Society (ACS)
Date: 02-09-2014
DOI: 10.1021/JO501501Z
Immunogenicity Assessment of Cell Wall Carbohydrates of Group A Streptococcus via Self-Adjuvanted Glyco-lipopeptides
Publisher: American Chemical Society (ACS)
Date: 03-02-2021
New PKS-NRPS tetramic acids and pyridinone from an Australian marine-derived fungus, Chaunopycnis sp.
Publisher: Royal Society of Chemistry (RSC)
Date: 2015
DOI: 10.1039/C5OB01058F
Abstract: Marine-derived fungus Chaunopycnis sp. yielded the tetramic acid F-14329 ( 1 ) and new analogues, chaunolidines A–C ( 2–4 ), together with the new pyridinone chaunolidone A ( 5 ), and pyridoxatin ( 6 ).
Kinase Inhibitor Scaffolds against Neurodegenerative Diseases from a Southern Australian Ascidian, Didemnum sp.
Publisher: Wiley
Date: 24-04-2012
Abstract: Screening a library of Southern Australian and Antarctic marine invertebrates and algae for inhibitors of neurodegenerative disease kinase targets casein kinase 1 (CK1δ), cyclin-dependent kinase 5 (CDK5) and glycogen synthase kinase 3β (GSK3β) identified a Western Australian Didemnum species (CMB-02127) as a high-priority specimen. Chemical fractionation returned the known aromatic alkaloids ningalins B-D as the major metabolites, together with six minor metabolites, the new ningalins E-G and the known hexacyclic pyrrole alkaloids lamellarins Z, G and A6. All structures were assigned by detailed spectroscopic analysis and literature comparisons, and the structural assignments were supported by biosynthetic considerations. The ningalins showed potent and broad inhibition across the three kinases, while the lamellarins were generally more selective for CDK5. Docking studies using published X-ray crystal structures of CDK5 revealed both scaffolds target the ATP binding pocket.
Lamellarins as Inhibitors of P‐Glycoprotein‐Mediated Multidrug Resistance in a Human Colon Cancer Cell Line
Publisher: Wiley
Date: 30-03-2012
Abstract: Chemical analysis of a Didemnum sp. (CMB-01656) collected during scientific Scuba operations off Wasp Island, New South Wales, yielded five new lamellarins A1 (1), A2 (2), A3 (3), A4 (4) and A5 (5) and eight known lamellarins C (6), E (7), K (8), M (9), S (10), T (11), X (12) and χ (13). Analysis of a second Didemnum sp. (CMB-02127) collected during scientific trawling operations along the Northern Rottnest Shelf, Western Australia, yielded the new lamellarin A6 (14) and two known lamellarins G (15) and Z (16). Structures were assigned to 1-16 on the basis of detailed spectroscopic analysis with comparison to literature data and authentic s les. Access to this unique library of natural lamellarins (1-16) provided a rare opportunity for structure-activity relationship (SAR) investigations, probing interactions between lamellarins and the ABC transporter efflux pump P-glycoprotein (P-gp) with a view to reversing multidrug resistance in a human colon cancer cell line (SW620 Ad300). These SAR studies, which were expanded to include the permethylated lamellarin derivative (17) and a series of lamellarin-inspired synthetic coumarins (19-24) and isoquinolines (25-26), successfully revealed 17 as a promising new non-cytotoxic P-gp inhibitor pharmacophore.
Spiralisones A–D: acylphloroglucinol hemiketals from an Australian marine brown alga, Zonaria spiralis
Publisher: Royal Society of Chemistry (RSC)
Date: 2012
DOI: 10.1039/C2OB26988K
Abstract: An intertidal s le of the Australian marine brown alga, Zonaria spiralis, exhibited promising kinase inhibitory and antibacterial activity. Chemical analysis returned six phloroglucinol-derived lipids, the new hemiketal spiralisones A-D (1-4) and the known chromones 5-6, and the known norsesquiterpenoid apo-9'-fucoxanthinone (7). Structures 1-7 were assigned on the basis of detailed spectroscopic analysis, biosynthetic considerations and total synthesis. Spiralisones undergo facile acid-mediated dehydration to yield the corresponding chromones, revealing for the first time that brown algal chromones may be handling artifacts rather than natural products. Hemiketals 1 and 2, and chromone 6, displayed inhibitory activity against the neurodegenerative disease kinase targets CDK5 25, CK1δ and GSK3β, while hemiketals 1, 3 and 4, and chromone 6, displayed growth inhibitory activity against the Gram-positive bacteria Bacillus subtilis (ATCC 6051 and 6633). The promising kinase inhibitory and antibacterial properties of the Z. spiralis extract were attributed to the cumulative effect of many moderately potent phloroglucinol-derived lipid co-metabolites.
Poly(hydrophobic Amino Acids) and Liposomes for Delivery of Vaccine against Group A Streptococcus
Publisher: MDPI AG
Date: 29-07-2022
Abstract: Adjuvants and delivery systems are essential components of vaccines to increase immunogenicity against target antigens, particularly for peptide epitopes (poor immunogens). Emulsions, nanoparticles, and liposomes are commonly used as a delivery system for peptide-based vaccines. A Poly(hydrophobic amino acids) delivery system was previously conjugated to Group A Streptococcus (GAS)-derived peptide epitopes, allowing the conjugates to self-assemble into nanoparticles with self adjuvanting ability. Their hydrophobic amino acid tail also serves as an anchoring moiety for the peptide epitope, enabling it to be integrated into the liposome bilayer, to further boost the immunological responses. Polyleucine-based conjugates were anchored to cationic liposomes using the film hydration method and administered to mice subcutaneously. The polyleucine-peptide conjugate, its liposomal formulation, and simple liposomal encapsulation of GAS peptide epitope induced mucosal (saliva IgG) and systemic (serum IgG, IgG1 and IgG2c) immunity in mice. Polyleucine acted as a potent liposome anchoring portion, which stimulated the production of highly opsonic antibodies. The absence of polyleucine in the liposomal formulation (encapsulated GAS peptide) induced high levels of antibody titers, but with poor opsonic ability against GAS bacteria. However, the liposomal formulation of the conjugated vaccine was no more effective than conjugates alone self-assembled into nanoparticles.
New dictyodendrins as BACE inhibitors from a southern Australian marine sponge, Ianthella sp.
Publisher: Royal Society of Chemistry (RSC)
Date: 2012
DOI: 10.1039/C2RA20322G
Opsonic Activity of Conservative Versus Variable Regions of the Group A Streptococcus M Protein.
Publisher: MDPI AG
Date: 07-05-2020
Abstract: Group A Streptococcus (GAS) and GAS-associated infections are a global challenge, with no licensed GAS vaccine on the market. The GAS M protein is a critical virulence factor in the fight against GAS infection, and it has been a primary target for GAS vaccine development. Measuring functional opsonic antibodies against GAS is an important component in the clinical development path for effective vaccines. In this study, we compared the opsonic activity of two synthetic, self-adjuvanting subunit vaccines containing either the J8- or 88/30-epitope in Swiss outbred mice using intranasal administration. Following primary immunization and three boosts, sera were assessed for IgG activity using ELISA, and opsonization activity against seven randomly selected clinical isolates of GAS was measured. Vaccine constructs containing the conservative J8-epitope showed significant opsonic activity against six out of the seven GAS clinical isolates, while the vaccine containing the variable 88/30-epitope did not show any significant opsonic activity.
Fascioquinols A–F: bioactive meroterpenes from a deep-water southern Australian marine sponge, Fasciospongia sp.
Publisher: Elsevier BV
Date: 04-2011
Amycolatopsins A–C: antimycobacterial glycosylated polyketide macrolides from the Australian soil Amycolatopsis sp. MST-108494
Publisher: Springer Science and Business Media LLC
Date: 25-10-2017
DOI: 10.1038/JA.2017.119
Abstract: A southern Australian soil isolate, Amycolatopsis sp. MST-108494, was subjected to a panel of fermentation and media optimization trials, supported by analytical chemical profiling, to detect and enhance production of a rare class of secondary metabolites. Chemical fractionation of two complementary fermentations yielded three new polyketides, identified by detailed spectroscopic analysis as the glycosylated macrolactones, amycolatopsins A (1), B (2) and C (3), closely related to the ammocidins and apoptolidins. Amycolatopsins 1 and 3 selectively inhibited growth of Mycobacterium bovis (BCG) and Mycobacterium tuberculosis (H37Rv) when compared with other Gram-positive or Gram-negative bacteria, with 3 exhibiting low levels of cytotoxicity toward mammalian cells. Thus, our data reveal promising structure activity relationship correlations where the antimycobacterial properties of amycolatopsins are enhanced by hydroxylation of the 6-Me (that is, 1 and 3), whereas mammalian cytotoxicity is decreased by hydrolysis of the disaccharide moiety (that is, 3).
Structural and stereochemical investigations into bromotyrosine-derived metabolites from southern Australian marine sponges, Pseudoceratina spp.
Publisher: Elsevier BV
Date: 11-2012
Divirensols: Sesquiterpene Dimers from the Australian Termite Nest-Derived Fungus Trichoderma virens CMB-TN16
Publisher: American Chemical Society (ACS)
Date: 31-12-2018
DOI: 10.1021/ACS.JNATPROD.8B00746
Abstract: A chemical investigation of the Australian termite nest-derived fungus Trichoderma virens CMB-TN16 yielded the known sesquiterpene gliocladic acid (1), together with two new acetylated analogues, 3-acetylgliocladic acid (2) and 14-acetylgliocladic acid (3), and seven new dimeric congeners, irensols A-G (4-10). All metabolites were identified by detailed spectroscopic analysis, supported by biosynthetic considerations, and were assessed for antibacterial and cytotoxic properties. The irensols are ex les of an exceptionally rare class of dimeric sesquiterpene, likely linked via a highly convergent biosynthetic pathway. HPLC-DAD-MS analysis of the crude fungal extract detected ions attributed to putative monomeric biosynthetic precursors.
Lipopolysaccharide (LPS) stimulation of fungal secondary metabolism
Publisher: Informa UK Limited
Date: 03-07-2014
Cholic Acid-based Delivery System for Vaccine Candidates against Group A Streptococcus.
Publisher: American Chemical Society (ACS)
Date: 24-07-2019
Structure–Activity Analysis of Cyclic Multicomponent Lipopeptide Self-Adjuvanting Vaccine Candidates Presenting Group A Streptococcus Antigens
Publisher: American Chemical Society (ACS)
Date: 29-04-2020
Precursor-Directed Biosynthesis Mediated Amplification of Minor Aza Phenylpropanoid Piperazines in an Australian Marine Fish-Gut-Derived Fungus, Chrysosporium sp. CMB-F214
Publisher: MDPI AG
Date: 25-08-2021
DOI: 10.3390/MD19090478
Abstract: Chemical analysis of an M1 agar plate cultivation of a marine fish-gut-derived fungus, Chrysosporium sp. CMB-F214, revealed the known chrysosporazines A–D (11–14) in addition to a suite of very minor aza analogues 1–6. A microbioreactor (MATRIX) cultivation profiling analysis failed to deliver cultivation conditions that significantly improved the yields of 1–6 however, it did reveal that M2 agar cultivation produced the new natural product 15. A precursor-directed biosynthesis strategy adopting supplementation of a CMB-F214 M1 solid agar culture with sodium nicotinate enhanced production of otherwise inaccessible azachrysposorazines A1 (1), A2 (2), B1 (3), C1 (4), C2 (5) and D1 (6), in addition to four new chrysosporazines chrysosporazines N–P (7–9) and spirochrysosporazine A (10). Structures inclusive of absolute configurations were assigned to 1–15 based on detailed spectroscopic and chemical analyses, and biosynthetic considerations. Non-cytotoxic to human carcinoma cells, azachrysosporazies 1–5 were capable of reversing doxorubicin resistance in P-glycoprotein (P-gp)-overexpressing human colon carcinoma cells (SW620 Ad300), with optimum activity exhibited by the C-2′ substituted analogues 3–5.
Poly(amino acids) as a potent self-adjuvanting delivery system for peptide-based nanovaccines.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 31-01-2020
Abstract: A new vaccine immunostimulatory (adjuvant) system was developed based on fully defined polymers built from native amino acids.
Reveromycins Revealed: New polyketidespiroketals from Australian marine-derived and terrestrial Streptomyces spp. A case of natural productsvs. artifacts
Publisher: Royal Society of Chemistry (RSC)
Date: 2011
DOI: 10.1039/C0OB00654H
Abstract: Chemical analysis of fermentation products from two Australian Streptomyces isolates yielded all four known and twelve new ex les of the rare reveromycin class of polyketide spiroketals, including hemi-succinates, hemi-fumarates and hemi-furanoates. Reveromycins were identified with the aid of HPLC-DAD-MS and HPLC-DAD-SPE-NMR methodology, and structures were assigned by detailed spectroscopic analysis. The structural and mechanistic requirements for an unprecedented hemi-succinate : ketal-succinyl equilibrium were defined and provided a basis for proposing that reveromycin 4'-methyl esters and 5,6-spiroketals were artifacts. A plausible reveromycin polyketide biosynthesis is proposed, requiring a 2-methylsuccinyl-CoA starter unit, with flexible incorporation of a C(6-8) polyketide chain extension and diacid esterification units. Structure activity relationship investigations by co-metabolites were used to assess the anticancer, antibacterial and antifungal properties of reveromycins.
Polyacrylate-Peptide Antigen Conjugate as a Single-Dose Oral Vaccine against Group A Streptococcus.
Publisher: MDPI AG
Date: 13-01-2020
Abstract: Group A Streptococcus (GAS)-associated rheumatic heart disease is a leading cause of death caused by GAS infection. While antibiotics can treat the infection in most cases, growing antibiotic resistance, late medical intervention, and recurrent infection are major obstacles to the effective treatment of GAS-associated diseases. As GAS infection typically originates from the bacterial colonization of mucosal tissue in the throat, an oral vaccine that can generate both systemic and mucosal immune responses would solve problems associated with traditional medical interventions. Moreover, orally delivered vaccines are more easily administered and less expensive for mass immunization. In this study, the B-cell epitope J8, derived from GAS M protein, and universal T-helper Pan HLA-DR-binding epitope peptide (PADRE), were conjugated to poly (methyl acrylate) (PMA) to form a self-assembled nanoparticle vaccine candidate (PMA-P-J8). Strong systemic and mucosal immune responses were induced upon single oral immunization of mice with the conjugate. The antibodies generated were opsonic against GAS clinical isolates as measured after boost immunization. Thus, we developed a simple conjugate as an effective, adjuvant-free oral peptide-based vaccine.
Structure-Activity Relationships of Wollamide Cyclic Hexapeptides with Activity against Drug-Resistant and Intracellular Mycobacterium tuberculosis.
Publisher: American Society for Microbiology
Date: 03-2019
DOI: 10.1128/AAC.01773-18
Abstract: Wollamides are cyclic hexapeptides, recently isolated from an Australian soil Streptomyces isolate, that exhibit promising in vitro antimycobacterial activity against Mycobacterium bovis Bacille Calmette Guérin without displaying cytotoxicity against a panel of mammalian cells. Here, we report the synthesis and antimycobacterial activity of 36 new synthetic wollamides, collated with all known synthetic and natural wollamides, to reveal structure characteristics responsible for in vitro growth-inhibitory activity against Mycobacterium tuberculosis (H37Rv, H37Ra, CDC1551, HN878, and HN353).
Cytochalasins from an Australian Marine Sediment-Derived Phomopsis sp (CMB-M0042F): Acid-Mediated Intramolecular Cycloadditions Enhance Chemical Diversity
Publisher: American Chemical Society (ACS)
Date: 31-08-2017
Abstract: Chemical analysis of an Australian coastal marine sediment-derived fungus, Phomopsis sp. (CMB-M0042F), yielded the known cytochalasins J (1) and H (2), together with five new analogues, cytochalasins J
Mollemycin A: an antimalarial and antibacterial glyco-hexadepsipeptide-polyketide from an Australian marine-derived Streptomyces sp. (CMB-M0244).
Publisher: American Chemical Society (ACS)
Date: 11-03-2014
DOI: 10.1021/OL5003913
Abstract: A marine-derived Streptomyces sp. (CMB-M0244) isolated from a sediment collected off South Molle Island, Queensland, produced mollemycin A (1) as a new first in class glyco-hexadepsipeptide-polyketide. The structure of 1 was assigned by detailed spectroscopic analysis, supported by chemical derivatization and degradation, and C3 Marfey's analysis. Mollemycin A (1) exhibits exceptionally potent and selective growth inhibitory activity against Gram-positive and Gram-negative bacteria (IC50 10-50 nM) and drug-sensitive (3D7 IC50 7 nM) and multidrug-resistant (Dd2 IC50 9 nM) clones of the malaria parasite Plasmodium falciparum.
9-(5'-Deoxy-5'-thio-β-D-xylofuranosyl)adenine Disulfide from the Southern Australian Marine Sponge Trachycladus laevispirulifer: the First Natural Occurrence of a Nucleoside Disulfide
Publisher: CSIRO Publishing
Date: 2010
DOI: 10.1071/CH09645
Abstract: Chemical fractionation of a southern Australian marine sponge, Trachycladus laevispirulifer, yielded 9-(5′-deoxy-5′-thio-β-d-xylofuranosyl)adenine disulfide as the first recorded natural occurrence of a nucleoside disulfide, and only the second of a xylo-nucleoside. Structure elucidation of the disulfide was achieved by detailed spectroscopic analysis and comparison to synthetic model compounds. The antibacterial, antifungal, and anticancer properties of the disulfide are documented and the literature surrounding natural and synthetic thionucleosides is reviewed.
Neobulgarones Revisited: Anti and Syn Bianthrones from an Australian Mud Dauber Wasp Nest-Associated Fungus, Penicillium sp. CMB-MD22
Publisher: American Chemical Society (ACS)
Date: 03-02-2021
DOI: 10.1021/ACS.JNATPROD.0C01035
Abstract: We report on the chemical analysis of a mud dauber wasp nest-associated fungus,
Structure Revision of Penipacids A–E Reveals a Putative New Cryptic Natural Product, N-aminoanthranilic Acid, with Potential as a Transcriptional Regulator of Silent Secondary Metabolism
Publisher: MDPI AG
Date: 24-05-2022
DOI: 10.3390/MD20060339
Abstract: Reconsideration of the spectroscopic data for penipacids A–E, first reported in 2013 as the acyclic amidines 1–5 from the South China deep sea sediment-derived fungus Penicillium paneum SD-44, prompted a total synthesis structure revision as the hydrazones 6–10. This revision strongly supported the proposition that penipacids A–B (6–7) were artifact Schiff base adducts of the cryptic (undetected) natural product N-aminoanthranilic acid (11) with diacetone alcohol, induced by excessive exposure to acetone and methanol under acidic handling conditions. Likewise, the revised structures for penipacids C–D (8–9) and E (10) raise the possibility that they may also be artifact Schiff base adducts of 11 and the media constituents pyruvic acid and furfural, respectively. A review of the natural products literature revealed other Schiff base (hydrazone) natural products that might also be viewed as Schiff base adduct artifacts of 11. Having raised the prospect that 11 is an undetected and reactive cryptic natural product, we went on to establish that 11 is not cytotoxic to a range of bacterial, fungal or mammalian (human) cell types. Instead, when added as a supplement to microbial cultivations, 11 can act as a chemical cue/transcriptional regulator, activating and/or enhancing the yield of biosynthetic gene clusters encoding for other natural product chemical defenses. This study demonstrates the value of challenging the structure and artifact status of natural products, as a window into the hidden world of cryptic and highly reactive natural products.
Poly(hydrophobic amino acid)-Based Self-Adjuvanting Nanoparticles for Group A Streptococcus Vaccine Delivery
Publisher: American Chemical Society (ACS)
Date: 02-02-2021
Self-assembly of trimethyl chitosan and poly(anionic amino acid)-peptide antigen conjugate to produce a potent self-adjuvanting nanovaccine delivery system
Publisher: Elsevier BV
Date: 07-2019
DOI: 10.1016/J.BMC.2019.05.033
Abstract: Short peptides derived from virulent pathogen proteins are promising antigens for the development of vaccines against infectious diseases. However, in order to mimic the danger signals associated with natural infection and stimulate an adaptive immune response, peptide antigens must be co-delivered with immune adjuvants. In this study, a group A streptococcus (GAS) M-protein derived B-cell epitope: J8, and universal T-helper epitope P25 containing peptides, were chemically coupled with different anionic amino acid-based polymers. The poly(anionic amino acid)-peptide antigen conjugates were mixed with trimethyl chitosan (TMC) to produce self-adjuvanting nanoparticulate vaccine candidates. TMC from two different sources were used to analyse their effect on immunogenicity. The nanoparticles produced from a peptide modified with 10 residues of polyglutamic acid and fungal TMC (NP5) stimulated production of the highest levels of serum antibodies in outbred mice. These antibodies were opsonic against all clinical GAS isolates tested.
Structure-activity relationship of group A streptococcus lipopeptide vaccine candidates in trimethyl chitosan-based self-adjuvanting delivery system
Publisher: Elsevier BV
Date: 10-2019
DOI: 10.1016/J.EJMECH.2019.06.047
Abstract: Synthetic peptide vaccines based on epitopes derived from the conserved region of M-protein are proving to be a realistic option for protection against group A streptococcus (GAS). However, peptide epitopes alone are poorly immunogenic due to lack of pathogen-associated structural patterns. Therefore, we developed a GAS peptide vaccine based on combined lipidic TLR 2 agonist and self-adjuvanting polymers. We synthesized three α-poly-l-glutamic acid (PGA) conjugated lipopeptides composed of 2-amino-d,l-hexadecanoic acid, GAS B-cell peptide epitope J8 (QAEDKVKQSREAKKQVEKALKQLEDKVQ) and universal T-helper epitope PADRE (AKFVAAWTLKAAA) in different spatial arrangements. The anionic lipopeptide conjugates formed nanoparticles via ionic-complexation with a cationic polymer, trimethyl chitosan (TMC). We demonstrated that the spatial arrangement of vaccine components has a significant influence on peptide conformation and particle formation and, as such, contributes to the differential efficacy and opsonin-mediated killing potential of nanovaccines. Nanoparticles carrying branched helical lipopeptide with T-helper epitope on free N-termini (NP3) stimulated the most potent humoral immune responses. Lipopeptides without TMC (LP1-LP3) and TMC nanoparticles of peptide alone (without lipid) NP (P1) were poor inducers of antibody production, indicating that both TMC and lipid are required to induce a strong opsonic immune response.
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