期刊
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
卷 132, 期 44, 页码 15661-15670出版社
AMER CHEMICAL SOC
DOI: 10.1021/ja105825a
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资金
- NIH [GM077516, MSTP GM07739]
- Howard Hughes Medical Institute
- Beckman Foundation
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.
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