ORCID Profile
0000-0003-2850-7797
Current Organisation
University of San Agustin
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: American Chemical Society (ACS)
Date: 05-03-2010
DOI: 10.1021/OL100249V
Publisher: Wiley
Date: 26-05-2009
Publisher: Wiley
Date: 27-08-2009
Publisher: MDPI AG
Date: 23-03-2022
Abstract: Cajanus cajan L. (pigeon pea, locally known in the Philippines as kadios) seed is a functional food with health benefits that extend beyond their nutritional value. C. cajan seeds contain highly erse secondary metabolites with enriched beneficial properties, such as antibacterial, anticancer, and antioxidant activities. However, the antibacterial activities of secondary metabolites from Philippine-grown C. cajan, against multidrug-resistant Staphylococcus aureus have not been thoroughly described. Here, we investigated the in vitro antibacterial properties of C. cajan seed against multidrug-resistant S. aureus ATCC BAA-44 (MDRSA) and three other S. aureus strains (S. aureus ATCC 25923, S. aureus ATCC 6538, and coagulase-negative S. aureus) and, subsequently, identified the antibiotic markers against S. aureus strains using mass spectrometry. Secondary metabolites from C. cajan seeds were extracted using acetone, methanol, or 95% ethanol. Antibacterial screening revealed antibiotic activity for the C. cajan acetone extract. Bioassay-guided purification of the C. cajan acetone extract afforded three semi-pure high-performance liquid chromatography (HPLC) fractions exhibiting 32–64 µg/mL minimum inhibitory concentration (MIC) against MDRSA. Chemical profiling of these fractions using liquid chromatography mass spectrometry (LCMS) identified six compounds that are antibacterial against MDRSA. High-resolution mass spectrometry (HRMS), MS/MS, and dereplication using Global Natural Products Social Molecular Networking (GNPS)™, and National Institute of Standards and Technology (NIST) Library identified the metabolites as rhein, formononetin, laccaic acid D, crotafuran E, ayamenin A, and biochanin A. These isoflavonoids, anthraquinones, and pterocarpanoids from C. cajan seeds are potential bioactive compounds against S. aureus, including the multidrug-resistant strains.
Publisher: American Chemical Society (ACS)
Date: 02-2016
Abstract: Nahuoic acids A-E (1-5) have been isolated from laboratory cultures of a Streptomyces sp. obtained from a tropical marine sediment. The structures of the new polyketides 2-5 were elucidated by analysis of spectroscopic data of the natural products and the chemical derivatives 6 and 7. Nahuoic acids 1-5 are in vitro inhibitors of the histone methyltransferase SETD8, and nahuoic acid A (1) and its pentaacetate derivative 8 inhibit the proliferation of several cancer cells lines in vitro with modest potency. At the IC50 for cancer cell proliferation, nahuoic acid A (1) showed selective inhibition of SETD8 in U2OS osteosarcoma cells that reflect its selectivity against a panel of pure histone methyl transferases. A cell cycle analysis revealed that the cellular toxicity of nahuoic acid A (1) is likely linked to its ability to inhibit SETD8 activity.
Publisher: American Chemical Society (ACS)
Date: 09-02-2016
DOI: 10.1021/ACS.JNATPROD.5B00951
Abstract: Cryptococcus gattii is a human pathogen and causative agent of a pernicious, sometimes fatal, disseminated fungal disease. Investigation of antifungal extracts of the marine sponge association Plakortis halichondrioides-Xestospongia deweerdtae and the sponge Plakortis zyggompha from the Bahamas led to the discovery and isolation of 6-epi-7,8-dihydroplakortide K (1), plakortide AA (2), and three new plakinic acids, N-P (4-6 unstable 1,2-dioxolanes bearing benzyl-substituted conjugated dienes), along with known plakinic acids L, K, and M.5 Chiroptical comparisons and DFT calculations of (13)C NMR chemical shifts were used to assign the absolute stereostructure of 4. The stereospecific base-promoted rearrangement-saponification of 1 to 10 was briefly investigated and showed tight kinetic control and stereospecific formation of the new C-2 stereocenter with inversion at C-3. Plakinic acid M and plakortides 9 and 11 exhibited antifungal activity against C. gattii (MIC90 = 2.4 to 36 μM), but plakinic acids N-P were inactive under the same conditions.
Publisher: MDPI AG
Date: 08-08-2023
DOI: 10.3390/PATHOGENS12081019
Abstract: In the Philippines, data are scarce on the co-occurrence of multiple β-lactamases (BLs) in clinically isolated Gram-negative bacilli. To investigate this phenomenon, we characterized BLs from various β-lactam-resistant Klebsiella pneumoniae, Escherichia coli, Acinetobacter baumannii, and Pseudomonas aeruginosa isolated from a Philippine tertiary care hospital. The selected Gram-negative bacilli (n = 29) were resistant to either third-generation cephalosporins (resistance category 1 (RC1)), cephalosporins and penicillin-β-lactamase inhibitors (RC2), or carbapenems (RC3). Isolates resistant to other classes of antibiotics but susceptible to early-generation β-lactams were also selected (RC4). All isolates underwent antibiotic susceptibility testing, disk-diffusion-based BL detection assays, and PCR with sequence analysis of extended-spectrum BLs (ESBLs), metallo-BLs, AmpC BLs, and oxacillinases. Among the study isolates, 26/29 harbored multi-class BLs. All RC1 isolates produced ESBLs, with blaCTX-M as the dominant (19/29) gene. RC2 isolates produced ESBLs, four of which harbored blaTEM plus blaOXA-1 or other ESBL genes. RC3 isolates carried blaNDM and blaIMP, particularly in three of the metallo-BL producers. RC4 Enterobacteriaceae carried blaCTX-M, blaTEM, and blaOXA-24-like, while A. baumannii and P. aeruginosa in this category carried either blaIMP or blaOXA-24. Genotypic profiling, in complement with phenotypic characterization, revealed multi-class BLs and cryptic metallo-BLs among β-lactam-resistant Gram-negative bacilli.
Publisher: Frontiers Media SA
Date: 24-04-2020
Publisher: Informa UK Limited
Date: 02-01-2014
Publisher: Public Library of Science (PLoS)
Date: 24-09-2008
Publisher: American Chemical Society (ACS)
Date: 02-04-2009
DOI: 10.1021/OL9004189
Abstract: Hemi-phorboxazole A, a minor truncated analogue of phorboxazole A from the marine sponge Phorbas sp., was isolated in a total yield of 16.5 microg (28 nmol). The structure was elucidated by application of integrated nanomole-scale natural product techniques, including cryomicroprobe NMR, (1)H-coupled HSQC, and circular dichroism (CD).
Publisher: Public Library of Science (PLoS)
Date: 30-06-2016
Publisher: MDPI AG
Date: 31-07-2021
DOI: 10.3390/MD19080441
Abstract: Marine sediments host erse actinomycetes that serve as a source of new natural products to combat infectious diseases and cancer. Here, we report the bio ersity, bioactivities against ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) and ovarian cancer, and metabolites variation among culturable actinomycetes isolated from the marine sediments of Visayan Sea, Philippines. We identified 15 Streptomyces species based on a 16S rRNA gene sequence analysis. The crude extracts of 10 Streptomyces species have inhibited the growth of ESKAPE pathogens with minimum inhibitory concentration (MIC) values ranging from 0.312 mg/mL to 20 mg/mL depending on the strain and pathogens targeted. Additionally, ten crude extracts have antiproliferative activity against A2780 human ovarian carcinoma at 2 mg/mL. To highlight, we observed that four phylogenetically identical Streptomyces albogriseolus strains demonstrated variation in antibiotic and anticancer activities. These strains harbored type I and II polyketide synthase (PKS) and non-ribosomal synthetase (NRPS) genes in their genomes, implying that their bioactivity is independent of the polymerase chain reaction (PCR)-detected bio-synthetic gene clusters (BGCs) in this study. Metabolite profiling revealed that the taxonomically identical strains produced core and strain-specific metabolites. Thus, the chemical ersity among these strains influences the variation observed in their biological activities. This study expanded our knowledge on the potential of marine-derived Streptomyces residing from the unexplored regions of the Visayan Sea as a source of small molecules against ESKAPE pathogens and cancer. It also highlights that Streptomyces species strains produce unique strain-specific secondary metabolites thus, offering new chemical space for natural product discovery.
Publisher: Elsevier BV
Date: 04-2010
Publisher: Wiley
Date: 26-05-2009
Publisher: American Chemical Society (ACS)
Date: 02-03-2009
DOI: 10.1021/NP8007649
Publisher: American Chemical Society (ACS)
Date: 21-10-2008
DOI: 10.1021/OL802065D
Publisher: Wiley
Date: 30-10-2009
DOI: 10.1007/S11745-009-3360-0
Abstract: Isorhizochalin (1) was isolated as its peracetate from the EtOH extract of the sponge Rhizochalina incrustata. Its structure and absolute stereochemistry were elucidated as (2S,3R,26R,27R)-2,27-diamino-3-O-beta-D: -galactopyranosyl-oxy-26-hydroxyoctacosan-18-one by extensive NMR, MS studies, chemical transformations, including micromolar-scale Baeyer-Villiger oxidation, and by analysis of CD spectra of isorhizochalinin perbenzoate (2b). Isorhizochalin is an unprecedented C-2 epimer of rhizochalin having an erythro configuration at the glycosylated 2-amino-3-alkanol alpha-terminus in contrast with a canonical threo configuration for other representatives of this structural group. Probable biogenesis of 1 is discussed in the context of known sphingolipid biosynthesis beginning with condensation of alanine with a fatty acyl CoA thioester. The aglycone, isorhizochalinin (2a), shows cytotoxicity against human leukemia HL-60 and THP-1 cells with IC(50) values of 2.90 and 2.20 microM, respectively.
Publisher: American Chemical Society (ACS)
Date: 12-07-2011
DOI: 10.1021/OL2014494
Publisher: Elsevier BV
Date: 06-2009
Publisher: Microbiology Society
Date: 10-2006
Abstract: This study demonstrates that attachment of the marine bacterium Pseudoalteromonas tunicata to the cellulose-containing surface of the green alga Ulva australis is mediated by a mannose-sensitive haemagglutinin (MSHA-like) pilus. We have identified an MSHA pilus biogenesis gene locus in P. tunicata , termed mshI1I2JKLMNEGFBACDOPQ , which shows significant homology, with respect to its genetic characteristics and organization, to the MSHA pilus biogenesis gene locus of Vibrio cholerae . Electron microscopy studies revealed that P. tunicata wild-type cells express flexible pili peritrichously arranged on the cell surface. A P. tunicata mutant (SM5) with a transposon insertion in the mshJ region displayed a non-piliated phenotype. Using SM5, it has been demonstrated that the MSHA pilus promotes attachment of P. tunicata wild-type cells in polystyrene microtitre plates, as well as to microcrystalline cellulose and to the living surface of U. australis . P. tunicata also demonstrated increased pilus production in response to cellulose and its monomer constituent cellobiose. The MSHA pilus thus functions as a determinant of attachment in P. tunicata , and it is proposed that an understanding of surface sensing mechanisms displayed by P. tunicata will provide insight into specific ecological interactions that occur between this bacterium and higher marine organisms.
Publisher: Elsevier BV
Date: 05-2015
DOI: 10.1016/J.PHYTOCHEM.2014.10.013
Abstract: Continually exposed to potential pathogens, vascular plants have evolved intricate defense mechanisms to recognize encroaching threats and defend themselves. They do so by inducing a set of defense responses that can help defeat and/or limit effects of invading pathogens, of which the non-host disease resistance response is the most common. In this regard, pea (Pisum sativum) pod tissue, when exposed to Fusarium solani f. sp. phaseoli spores, undergoes an inducible transcriptional activation of pathogenesis-related genes, and also produces (+)-pisatin, its major phytoalexin. One of the inducible pathogenesis-related genes is Disease Resistance Response-206 (DRR206), whose role in vivo was unknown. DRR206 is, however, related to the dirigent protein (DP) family. In this study, its biochemical function was investigated in planta, with the metabolite associated with its gene induction being pinoresinol monoglucoside. Interestingly, both pinoresinol monoglucoside and (+)-pisatin were co-localized in pea pod endocarp epidermal cells, as demonstrated using matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging. In addition, endocarp epidermal cells are also the site for both chalcone synthase and DRR206 gene expression. Taken together, these data indicate that both (+)-pisatin and pinoresinol monoglucoside function in the overall phytoalexin responses.
Publisher: Public Library of Science (PLoS)
Date: 10-10-2013
Publisher: MDPI AG
Date: 02-06-2022
DOI: 10.3390/MOLECULES27113569
Abstract: Laboratory cultures of two ‘biosynthetically talented’ bacterial strains harvested from tropical and temperate Pacific Ocean sediment habitats were examined for the production of new natural products. Cultures of the tropical Salinispora arenicola strain RJA3005, harvested from a PNG marine sediment, produced salinorcinol (3) and salinacetamide (4), which had previously been reported as products of engineered and mutated strains of Amycolatopsis mediterranei, but had not been found before as natural products. An S. arenicola strain RJA4486, harvested from marine sediment collected in the temperate ocean waters off British Columbia, produced the new aminoquinone polyketide salinisporamine (5). Natural products 3, 4, and 5 are putative shunt products of the widely distributed rifamycin biosynthetic pathway.
Publisher: Elsevier BV
Date: 09-2010
Publisher: American Chemical Society (ACS)
Date: 21-01-2009
DOI: 10.1021/NP800549N
Publisher: Springer Science and Business Media LLC
Date: 19-12-2008
DOI: 10.1038/NRD2487
Abstract: Drug discovery from marine natural products has enjoyed a renaissance in the past few years. Ziconotide (Prialt Elan Pharmaceuticals), a peptide originally discovered in a tropical cone snail, was the first marine-derived compound to be approved in the United States in December 2004 for the treatment of pain. Then, in October 2007, trabectedin (Yondelis PharmaMar) became the first marine anticancer drug to be approved in the European Union. Here, we review the history of drug discovery from marine natural products, and by describing selected ex les, we examine the factors that contribute to new discoveries and the difficulties associated with translating marine-derived compounds into clinical trials. Providing an outlook into the future, we also examine the advances that may further expand the promise of drugs from the sea.
Publisher: Wiley
Date: 30-12-2010
Publisher: Wiley
Date: 29-09-2008
Publisher: Elsevier BV
Date: 08-2013
DOI: 10.1016/J.CHEMBIOL.2013.06.013
Abstract: Padanamides are linear tetrapeptides notable for the absence of proteinogenic amino acids in their structures. In particular, two unusual heterocycles, (S)-3-amino-2-oxopyrrolidine-1-carboxamide (S-Aopc) and (S)-3-aminopiperidine-2,6-dione (S-Apd), are found at the C-termini of padanamides A and B, respectively. Here we identify the padanamide biosynthetic gene cluster and carry out systematic gene inactivation studies. Our results show that padanamides are synthesized by highly dissociated hybrid nonribosomal peptide synthetase olyketide synthase machinery. We further demonstrate that carbamoyltransferase gene padQ is critical to the formation of padanamide A but dispensable for biosynthesis of padanamide B. Biochemical investigations show that PadQ carbamoylates the rare biosynthetic precursor l-2,4-diaminobutyrate, generating l-2-amino-4-ureidobutyrate, the presumed precursor to the C-terminal residue of padanamide A. By contrast, the C-terminal residue of padanamide B may derive from glutamine. An unusual thioesterase-catalyzed cyclization is proposed to generate the S-Aopc/S-Apd heterocycles.
Publisher: American Chemical Society (ACS)
Date: 25-02-2010
DOI: 10.1021/NP1000297
Publisher: Georg Thieme Verlag KG
Date: 07-2012
Publisher: Royal Society of Chemistry (RSC)
Date: 2015
DOI: 10.1039/C5CC00882D
Abstract: A designed, dimeric analogue of TAT-peptide translocates through HeLa and primary neuronal cell membrane in a non-linear dependence on concentration.
Publisher: Elsevier BV
Date: 03-2010
Publisher: American Chemical Society (ACS)
Date: 20-08-2009
DOI: 10.1021/OL9014317
Publisher: Public Library of Science (PLoS)
Date: 20-11-2015
Publisher: American Chemical Society (ACS)
Date: 15-05-2009
DOI: 10.1021/JA9024929
Abstract: Muironolide A, a new chemical entity with an unprecedented chlorinated hexahydro-1H-isoindolone skeleton, was isolated in only 90 microg yield from the same marine sponge, Phorbas sp. that also provided phorboxazoles A and B. The structure was solved by interpretation of NMR data obtained at 600 MHz with a 1.7 mm cryo-microprobe in combination with FTMS, exciton coupled CD, and stereochemical correlation with authentic standards prepared by Reformatsky reaction of (-)-(1R,2S)-2-chloro-1-cyclopropanecarboxaldehyde. The absolute configuration of the chlorocyclopropane ring in 1 is opposite to that of co-occurring phorbasides A-F. Muironolide A is the first described macrolide bearing an esterified trichloromethyl carbinol, and may be produced by a cyanobacterium that also makes phorbasides.
Publisher: American Chemical Society (ACS)
Date: 11-07-2011
DOI: 10.1021/OL2017752
Publisher: MDPI AG
Date: 17-03-2021
DOI: 10.3390/MOLECULES26061688
Abstract: Honey exhibits antibacterial and antioxidant activities that are ascribed to its erse secondary metabolites. In the Philippines, the antibacterial and antioxidant activities, as well as the bioactive metabolite contents of the honey, have not been thoroughly described. In this report, we investigated the in vitro antibacterial and antioxidant activities of honey from Apis mellifera and Tetragonula biroi, identified the compound responsible for the antibacterial activity, and compared the observed bioactivities and metabolite profiles to that of Manuka honey, which is recognized for its antibacterial and antioxidant properties. The secondary metabolite contents of honey were extracted using a nonionic polymeric resin followed by antibacterial and antioxidant assays, and then spectroscopic analyses of the phenolic and flavonoid contents. Results showed that honey extracts produced by T. biroi exhibits antibiotic activity against Staphylococcal pathogens as well as high antioxidant activity, which are correlated to its high flavonoid and phenolic content as compared to honey produced by A. mellifera. The bioassay-guided fractionation paired with Liquid Chromatography Mass Spectrometry (LCMS) and tandem MS analyses found the presence of the flavonoid isorhamnetin (3-methylquercetin) in T. biroi honey extract, which was demonstrated as one of the compounds with inhibitory activity against multidrug-resistant Staphylococcus aureus ATCC BAA-44. Our findings suggest that Philippine honey produced by T. biroi is a potential nutraceutical that possesses antibiotic and antioxidant activities.
Publisher: SAGE Publications
Date: 2022
DOI: 10.1177/2515690X221103304
Abstract: Honey has a long history of therapeutic properties for multiple diseases, including inflammation and oxidative stress. This review aimed to provide a better understanding and renewed interest in the potential role of honey in obesity control, obesity-related diseases treatment and weight management, with specific reference to its components and the effect of honey overall. There is compelling evidence that honey possesses the desired properties for this purpose, as seen in the in vitro, in silico, in vivo and clinical analyses discussed in this review. This review also highlights the components potentially responsible for the health benefits of honey. Honey and its components reduce blood sugar levels, improve insulin sensitivity and lipid metabolism by reducing triglycerides, and reduce total cholesterol and LDL levels while increasing HDL levels that prevent excessive weight gain and reduce the risk of obesity and its complications. Further controlled studies are necessary to validate the role of honey in the management of obesity, both as a preventive and as a therapeutic agent.
Publisher: MDPI AG
Date: 26-02-2021
DOI: 10.3390/MD19030126
Abstract: Oceanapiside (OPS), a marine natural product with a novel bifunctional sphingolipid structure, is fungicidal against fluconazole-resistant Candida glabrata at 10 μg/mL (15.4 μM). The fungicidal effect was observed at 3 to 4 h after exposure to cells. Cytological and morphological studies revealed that OPS affects the budding patterns of treated yeast cells with a significant increase in the number of cells with single small buds. In addition, this budding morphology was found to be sensitive in the presence of OPS. Moreover, the number of cells with single medium-sized buds and cells with single large buds were decreased significantly, indicating that fewer cells were transformed to these budding patterns, suggestive of inhibition of polarized growth. OPS was also observed to disrupt the organized actin assembly in C. glabrata, which correlates with inhibition of budding and polarized growth. It was also demonstrated that phytosphingosine (PHS) reversed the antifungal activity of oceanapiside. We quantified the amount of long chain-bases (LCBs) and phytoceramide from the crude extracts of treated cells using LC-ESI-MS. PHS concentration was elevated in extracts of cells treated with OPS when compared with cells treated with miconazole and hotericin B. Elevated levels of PHS in OPS-treated cells confirms that OPS affects the pathway at a step downstream of PHS synthesis. These results also demonstrated that OPS has a mechanism of action different to those of miconazole and hotericin B and interdicts fungal sphingolipid metabolism by specifically inhibiting the step converting PHS to phytoceramide.
Publisher: Elsevier BV
Date: 11-2011
Publisher: Royal Society of Chemistry (RSC)
Date: 2014
DOI: 10.1039/C4MB00403E
Abstract: Advanced metabolomics/metabolite imaging in situ , transcriptome sequencing, and bioinformatics enabled discovery and localization of a previously undetectable biochemical pathway to aporphine alkaloids in Podophyllum hexandrum / peltatum . This discovery settles a century old enigma.
Publisher: American Society for Microbiology
Date: 06-2004
DOI: 10.1128/AEM.70.6.3232-3238.2004
Abstract: The newly described green-pigmented bacterium Pseudoalteromonas tunicata (D2) produces target-specific inhibitory compounds against bacteria, algae, fungi, and invertebrate larvae and is frequently found in association with living surfaces in the marine environment. As part of our studies on the ecology of P. tunicata and its interaction with marine surfaces, we examined the ability of P. tunicata to form biofilms under continuous culture conditions within the laboratory. P. tunicata biofilms exhibited a characteristic architecture consisting of differentiated microcolonies surrounded by water channels. Remarkably, we observed a repeatable pattern of cell death during biofilm development of P. tunicata , similar to that recently reported for biofilms of Pseudomonas aeruginosa (J. S. Webb et al., J. Bacteriol. 185: 4585-4595, 2003). Killing and lysis occurred inside microcolonies, apparently resulting in the formation of voids within these structures. A subpopulation of viable cells was always observed within the regions of killing in the biofilm. Moreover, extensive killing in mature biofilms appeared to result in detachment of the biofilm from the substratum. A novel 190-kDa autotoxic protein produced by P. tunicata , designated AlpP, was found to be involved in this biofilm killing and detachment. A Δ alpP mutant derivative of P. tunicata was generated, and this mutant did not show cell death during biofilm development. We propose that AlpP-mediated cell death plays an important role in the multicellular biofilm development of P. tunicata and subsequent dispersal of surviving cells within the marine environment.
Publisher: American Chemical Society (ACS)
Date: 28-12-2012
DOI: 10.1021/OL303416K
Abstract: The histone lysine monomethyltransferase SETD8 is an epigenetic regulator of cell cycle progression. Nahuoic acid A (1), a polyketide produced in culture by a Streptomyces sp. obtained from a tropical marine sediment, is the first known selective SAM-competitive inhibitor of SETD8. The structure of nahuoic acid A (1) has been elucidated by chemical transformation and detailed analysis of spectroscopic data.
Publisher: Wiley
Date: 08-01-2009
Publisher: MDPI AG
Date: 12-11-2021
DOI: 10.3390/MD19110635
Abstract: Oceanalin B (1), an α,ω-bipolar natural product belonging to a rare family of sphingoid tetrahydoisoquinoline β-glycosides, was isolated from the EtOH extract of the lyophilized marine sponge Oceanapia sp. as the second member of the series after oceanalin A (2) from the same animal. The compounds are of particular interest due to their biogenetically unexpected structures as well as their biological activities. The structure and absolute stereochemistry of 1 as a α,ω-bifunctionalized sphingoid tetrahydroisoquinoline β-glycoside was elucidated using NMR, CD and MS spectral analysis and chemical degradation. Oceanalin B exhibited in vitro antifungal activity against Candidaglabrata with a MIC of 25 μg/mL.
Publisher: Wiley
Date: 20-06-2020
DOI: 10.1111/CBDD.13706
Publisher: American Society for Microbiology
Date: 13-04-2023
DOI: 10.1128/SPECTRUM.03661-22
Abstract: Streptomyces tubbatahanensis DSD3025 T is a novel actinomycete with antibiotic and anticancer activities from Tubbataha Reefs Natural Park, a United Nations Educational, Scientific and Cultural Organization World Heritage Site in Sulu Sea and considered one of the Philippines’ oldest and most-well-protected marine ecosystems. In silico genome mining tools were used to identify putative BGCs that led to the discovery of genes involved in the production of halogenated carbazole alkaloids and new natural products. By integrating bioinformatics-driven genome mining and metabolomics, we unearthed the hidden biosynthetic richness and mined the associated chemical entities from the novel Streptomyces species.
Publisher: American Chemical Society (ACS)
Date: 17-05-2015
DOI: 10.1021/ACS.JNATPROD.5B00023
Abstract: An integrated omics approach using genomics, transcriptomics, metabolomics (MALDI mass spectrometry imaging, MSI), and bioinformatics was employed to study spatiotemporal formation and deposition of health-protecting polymeric lignans and plant defense cyanogenic glucosides. Intact flax (Linum usitatissimum) capsules and seed tissues at different development stages were analyzed. Transcriptome analyses indicated distinct expression patterns of dirigent protein (DP) gene family members encoding (-)- and (+)-pinoresinol-forming DPs and their associated downstream metabolic processes, respectively, with the former expressed at early seed coat development stages. Genes encoding (+)-pinoresinol-forming DPs were, in contrast, expressed at later development stages. Recombinant DP expression and DP assays also unequivocally established their distinct stereoselective biochemical functions. Using MALDI MSI and ion mobility separation analyses, the pinoresinol downstream derivatives, secoisolariciresinol diglucoside (SDG) and SDG hydroxymethylglutaryl ester, were localized and detectable only in early seed coat development stages. SDG derivatives were then converted into higher molecular weight phenolics during seed coat maturation. By contrast, the plant defense cyanogenic glucosides, the monoglucosides linamarin/lotaustralin, were detected throughout the flax capsule, whereas diglucosides linustatin/neolinustatin only accumulated in endosperm and embryo tissues. A putative biosynthetic pathway to the cyanogens is proposed on the basis of transcriptome coexpression data. Localization of all metabolites was at ca. 20 μm resolution, with the web based tool OpenMSI enabling not only resolution enhancement but also an interactive system for real-time searching for any ion in the tissue under analysis.
Publisher: American Chemical Society (ACS)
Date: 06-02-2017
DOI: 10.1021/ACS.ORGLETT.6B03619
Abstract: The new ansa macrolide antibiotics 1 to 4 have been isolated from cultures of a Micromonospora sp. obtained from a marine sediment. Rifamycins 1 and 2 are the first natural ansa macrolides to have a 3-amino substituent. Sporalactams A (3) and B (4) are comprised of a heterocylic core 5 and a 14-membered ansa bridge that are both unprecedented. Sporalactam B (4) shows selective and potent inhibition of Mycobacterium tuberculosis.
Publisher: American Chemical Society (ACS)
Date: 05-11-2010
DOI: 10.1021/NP100470H
Abstract: A fractional factorial design approach has been used to enhance secondary metabolite production by two Penicillium strains. The method was initially used to improve the production of bioactive extracts as a whole and subsequently to optimize the production of particular bioactive metabolites. Enhancements of over 500% in secondary metabolite production were observed for both P. oxalicum and P. citrinum. Two new alkaloids, citrinalins A (5) and B (6), were isolated and identified from P. citrinum cultures optimized for production of minor metabolites.
Publisher: Public Library of Science (PLoS)
Date: 26-12-2013
Publisher: Wiley
Date: 09-10-2009
Publisher: MDPI AG
Date: 23-09-2020
DOI: 10.3390/JMSE8100734
Abstract: The Philippine archipelago is geographically positioned in the tropics with rich areas of marine bio ersity. Its marine sediments harbor actinomycetes that exhibit antibacterial activity. Screening of actinomycetes isolated from marine sediments collected near the coast of Islas de Gigantes, Iloilo showed one isolate that exhibited high activity against the multidrug-resistant Staphylococcus aureus (MRSA) strain carrying the Staphylococcal Cassette Chromosome mec (SCCmec) type 1 gene, a biomarker for drug resistance. The isolate was identified as Streptomyces sp. strain DSD011 based on its 16s rRNA and protein-coding genes (atpD, recA, rpoB, and trpB) sequences, and was found to be a new species of salt-tolerant marine Streptomyces. Further, the strain harbors both non-ribosomal peptide synthetase (NRPS) and type II polyketide synthase (PKS) in its genome. The targeted chromatographic isolation and chemical investigations by Liquid Chromatography Mass Spectrometry-Time of Flight (LCMS-TOF), tandem mass spectrometry (MS/MS), and Global Natural Product Social molecular networking (GNPS) of the antibiotics produced by the strain afforded the two polycyclic aromatic polyketide angucycline glycosides, fridamycin A (1) and fridamycin D (2), which are products of type II PKS biosynthesis. Compounds 1 and 2 displayed antibacterial activity against MRSA with minimum inhibitory concentration (MIC) of 500 μg/mL and 62.5 μg/mL, respectively. These results suggest that the underexplored marine sediments near the coast of Islas de Gigantes, Iloilo offer access to undiscovered Streptomyces species that are invaluable sources of antibiotic leads.
Publisher: American Chemical Society (ACS)
Date: 11-03-2009
DOI: 10.1021/NP900009B
Location: United States of America
Start Date: 2016
End Date: 2017
Funder: United States Agency for International Development
View Funded Activity