Natural products have an impressive history ofmedicinal significance. Two classes of natural products exhibiting greatdiversity in structure and bioactivity are the nonribosomal peptides (NRPs) andpolyketides (PKs). Their biosyntheses are carried out by nonribosomal peptide synthetases(NRPSs) and polyketide synthases (PKSs) that have enormous size (> 200 kDa)and multimodular architecture. We developed a proteomic method (PrISM) for detection of expressedNRPSs and PKSs that takes advantage of their size. Here we report the discoveryof a new hybrid NRPS/PKS naturalproduct from an environmental bacterial isolate using PrISM. SDS-PAGEfollowed by in-gel digestion and LC-MS/MS of the proteome resulted in theidentification of NRPS and PKS derived peptides, enabling design of PCR primers for amplifying regions of the codingsequence for one NRPS and three PKSproteins. The modular nature of the biosynthetic enzymes along with substratespecificity prediction allowed for targeted detection of the small molecule.

Discovery of a new hybrid NRPS/PKS natural product through a proteomics-based approach

241st National Meeting (2011)

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