Tailoring enzyme-rich environmental DNA clones: a source of enzymes for generating libraries of unnatural natural products

摘要

A detailed bioinformatics analysis of six glycopeptide biosynthetic gene clusters isolated from soil environmental DNA (eDNA) mega-libraries indicates that a subset of these gene clusters contains collections of tailoring enzymes that are predicted to result in the production of new glycopeptide congeners. In particular, sulfotransferases appear in eDNA derived gene clusters at a much higher frequency than would be predicted from the characterization of glycopeptides from cultured Actinomycetes. Enzymes found on tailoring enzyme-rich eDNA clones associated with these six gene clusters were used to produce a series of new sulfated glycopeptide derivatives in both in vitro and in vivo derivatization studies. The derivatization of known natural products with eDNA derived tailoring enzymes is likely to be a broadly applicable strategy for generating libraries of new natural product variants.