ORCID Profile
0000-0002-8955-1735
Current Organisations
University of California, San Diego
,
UC Riverside
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Publisher: American Chemical Society (ACS)
Date: 11-07-2023
Publisher: Cold Spring Harbor Laboratory
Date: 04-12-2022
DOI: 10.1101/2022.12.04.519019
Abstract: Antimicrobial resistance has emerged as an urgent global public health threat, and development of novel therapeutics for treating infections caused by multi-drug resistant bacteria is urgent. Staphylococcus aureus is a major human and animal pathogen, responsible for high levels of morbidity and mortality worldwide. The intracellular survival of S. aureus in macrophages contributes to immune evasion, dissemination, and resilience to antibiotic treatment. Here, we present a confocal fluorescence imaging assay for monitoring macrophage infection by GFP-tagged Staphylococcus aureus as a front-line tool to identify antibiotic leads. The assay was employed in combination with nanoscaled chemical analyses to facilitate the discovery of a novel, active rifamycin analogue. Our findings indicate a promising new approach to the identification of anti-microbial compounds with macrophage intracellular activity. The novel antibiotic identified here may represent a useful addition to our armoury in tackling the silent pandemic of antimicrobial resistance.
Publisher: Elsevier BV
Date: 11-2011
Publisher: Wiley
Date: 16-03-2020
Publisher: American Chemical Society (ACS)
Date: 13-07-2011
DOI: 10.1021/NP200323E
Publisher: Wiley
Date: 02-12-2019
Abstract: The discovery of biologically active small molecules requires sifting through large amounts of data to identify unique or unusual arrangements of atoms. Here, we develop, test and evaluate an atom‐based sort to identify novel features of secondary metabolites and demonstrate its use to evaluate novelty in marine microbial and sponge extracts. This study outlines an important ongoing advance towards the translation of autonomous systems to identify, and ultimately elucidate, atomic novelty within a complex mixture of small molecules.
Publisher: American Chemical Society (ACS)
Date: 30-12-2021
DOI: 10.1021/ACS.JNATPROD.1C01084
Abstract: As part of a collaborative biomedical investigation of actinomycete bacteria isolated from sediments collected along the northern coast of Egypt (Mediterranean Sea), we explored the antibacterial metabolites from a bacterium identified as a
Publisher: American Chemical Society (ACS)
Date: 12-02-2019
DOI: 10.1021/ACSCHEMBIO.8B01058
Abstract: Analysis of the full genome of an environmentally unique, halotolerant Streptomyces sp. strain GSL-6C, isolated from the Great Salt Lake, revealed a gene cluster encoding the biosynthesis of the salinipeptins, d-amino-acid-containing members of the rare linaridin subfamily of ribosomally synthesized and post-translationally modified peptides (RiPPs). The sequence organization of the unmodified amino acid residues in salinipeptins A-D (1-4) were suggested by genome annotation, and subsequently, their sequence and post-translational modifications were defined using a range of spectroscopic techniques and chemical derivatization approaches. The salinipeptins are unprecedented linaridins bearing nine d-amino acids, which are uncommon in RiPP natural products and are the first reported in the linaridin subfamily. Whole genome mining of GSL-6C did not reveal any homologues of the reported genes responsible for amino acid epimerization in RiPPs, inferring new epimerases may be involved in the conversion of l- to d-amino acids. In addition, the N-oxide and dimethylimidazolidin-4-one moieties in salinipeptins B and C, which are modified from N, N-dimethylalanine, are unknown in bacterial peptides. The three-dimensional structure of salinipeptin A, possessing four loops generated by significant hydrogen bonding, was established on the basis of observed nuclear Overhauser effect (NOE) correlations. This study demonstrates that integration of genomic information early in chemical analysis significantly facilitates the discovery and structure characterization of novel microbial secondary metabolites.
Location: United States of America
No related grants have been discovered for William Fenical.