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Antibiotics from microbes: converging to kill.

ABSTRACT: As genetically encoded small molecules, antibiotics are phenotypes that have resulted from mutation and natural selection. Advances in genetics, biochemistry, and bioinformatics have connected hundreds of antibiotics to the gene clusters that encode them, allowing these molecules to be analyzed using the tools of evolutionary biology. This review surveys examples of convergent evolution from microbially produced antibiotics, including the convergence of distinct gene clusters on similar phenotypes and the merger of distinct gene clusters into a single functional unit. Examining antibiotics through an evolutionary lens highlights the versatility of biosynthetic pathways, reveals lessons for combating antibiotic resistance, and provides an entry point for studying the natural roles of these natural products.

SUBMITTER: Fischbach MA

PROVIDER: S-EPMC3176294 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature

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Antibiotics from microbes: converging to kill.

Fischbach Michael A MA

Current opinion in microbiology 20090818 5

As genetically encoded small molecules, antibiotics are phenotypes that have resulted from mutation and natural selection. Advances in genetics, biochemistry, and bioinformatics have connected hundreds of antibiotics to the gene clusters that encode them, allowing these molecules to be analyzed using the tools of evolutionary biology. This review surveys examples of convergent evolution from microbially produced antibiotics, including the convergence of distinct gene clusters on similar phenotyp ...[more]

PMID: 19695947

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Project description:One of the largest concerns with world health today is still antibiotic resistance, which is making it imperative to find efficient alternatives as soon as possible. It has been demonstrated that microbes are reliable sources for the creation of therapeutic antibiotics. This research intends to investigate the endophytic microorganisms from several medicinal plants in Fenghuang Mountain (Jiangsu Province, China) and to discover new antibiotics from their secondary metabolites. A total of 269 endophytic strains were isolated from nine distinct medicinal plants. Taxonomic analysis revealed that there were 20 distinct species among these endophytes, with Streptomyces being the most common genus. Three of the target strains were chosen for scale-up fermentation after preliminary screening of antibacterial activities and the metabolomics investigation using LC-MS. These strains were Penicillium sp. NX-S-6, Streptomyces sp. YHLB-L-2 and Streptomyces sp. ZLBB-S-6. Twenty-three secondary metabolites (1-23), including a new sorbicillin analogue (1), were produced as a result of antibacterial activity-guided isolation. Through spectroscopic analysis using MS and NMR, the structures of yield compounds were clarified. According to antibacterial data, S. aureus or B. subtilis were inhibited to varying degrees by sorrentanone (3), emodic acid (8), GKK1032 B (10), linoleic acid (14), toyocamycin (17) and quinomycin A (21). The most effective antimicrobial agent against S. aureus, B. subtilis, E. coli and A. baumannii was quinomycin A (21). In addition, quinomycin A showed strong antifungal activity against Aspergillus fumigatus, Cryptococcus neoformans, and two clinical isolated strains Aspergillus fumigatus #176 and #339, with MIC as 16, 4, 16 and 16 µg/mL, respectively. This is the first time that bioprospecting of actinobacteria and their secondary metabolites from medicinal plants in Fenghuang Mountain was reported. The finding demonstrates the potential of endophytic microbes in medical plants to produce a variety of natural products. Endophytic microbes will be an important source for new antibiotics.

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Antibiotics from microbes: converging to kill.

Publications

Antibiotics from microbes: converging to kill.

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