Abstract
Complete genome sequencing of dozens of strains of the soil bacterium Rhodococcus has revealed the presence of many cryptic biosynthetic gene clusters, presumably dedicated to the production of small molecules. This has sparked a renewed interest in this underexplored member of the Actinobacteria as a potential source of new bioactive compounds. Reported here is the discovery of a potent inhibitory molecule produced by a newly isolated strain of Rhodococcus, strain MTM3W5.2. This small inhibitory molecule shows strong activity against all Rhodococcus species tested, including the veterinary pathogen R. equi, and some closely related genera. It is not active against other Gram positive or Gram negative bacteria. A screen of random transposon mutants identified a gene required to produce this inhibitory compound. This gene is a large multi-domain, type I polyketide synthase that is part of a very large multi-gene biosynthetic gene cluster in the chromosome of strain MTM3W5.2. The high resolution mass spectrum of a major chromatogram peak from a broth culture extract of MTM3W5.2 shows the presence of a compound at m/z 911.5490 atomic mass units. This compound is not detected in the culture extracts from a non-producing mutant strain of MTM3W5.2. A large gene cluster containing at least 14 different type I polyketide synthase genes is proposed to be required to synthesize this antibiotic-like compound.
Highlights
For decades there has been a decline in the discovery of new antibiotics that have a novel structure and mode of action and more likely to be effective against bacteria resistant to older line antibiotics
MTM3W5.2 was cultured from a lawn soil located in Morristown, Tennessee by the heat treatment method
DNA sequence analysis of the 16S ribosomal RNA gene indicates that strain MTM3W5.2 is most similar to the 16S rRNA sequence from R. maanshanensis strain M712 [17]
Summary
For decades there has been a decline in the discovery of new antibiotics that have a novel structure and mode of action and more likely to be effective against bacteria resistant to older line antibiotics. No new antibiotic “scaffold” was discovered between 1962 and 2000 [1]. Recent DNA sequencing of bacterial genomes has revealed many unknown genes apparently devoted to production of secondary metabolites Of Health Sciences (B.L.) and the dept. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript
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