Readily available microbial genome information has brought the renaissance to natural product research in the past decade. While we have witnessed the acceleration of connecting genes to molecules using a genome-guided approach, the process to unravel the innate biological function of a newly discovered natural product remains the same. Here we describe an alternative strategy by employing essential gene duplication to identify novel secondary metabolite biosynthetic pathway that allows for the direct prediction of its molecular target, simply based on bioinformatics. In this talk, we will disclose a newly discovered antibiotic biosynthetic pathway of a bacterial origin and use it as an example to illustrate the power of this approach, along with the identification of the molecular target of the antibiotic, its resistance mechanism by the native producer and the effect of such a metabolite to the physiology of related bacterial species.

Essential-gene-duplication–guided genome mining of natural product antibiotics: All at once from genes to molecule, target, and resistance mechanism

245th National Meeting (2013)

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