biostudies-literature00450Banik JJHoward Hughes Medical InstituteNIGMS NIH HHS15661-70https://www.ebi.ac.uk/biostudies/studies/S-EPMC3111151biostudies-literatureUnknown132(44)A detailed bioinformatics analysis of six glycopeptide biosynthetic gene clusters isolated from soil environmental DNA (eDNA) megalibraries 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.Journal of the American Chemical SocietyTailoring enzyme-rich environmental DNA clones: a source of enzymes for generating libraries of unnatural natural products.PMC3111151T32 GM007739R01 GM077516-05GM077516R01 GM077516GM07739Calle PYBanik JJCraig JWBrady SF45falseTailoring enzyme-rich environmental DNA clones: a source of enzymes for generating libraries of unnatural natural products.A detailed bioinformatics analysis of six glycopeptide biosynthetic gene clusters isolated from soil environmental DNA (eDNA) megalibraries 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.2010-01-01T00:00:00Z2010 Nov2024-11-13T10:04:09.42Z2019-03-26T23:29:42ZS-EPMC31111512094589510.1021/ja105825a