期刊
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
卷 53, 期 32, 页码 8503-8507出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201400478
关键词
biosynthesis; D-amino acids; enzymes; natural products; peptides
资金
- SNF [31003A_146992/1]
- EU (BlueGenics and SYN PEPTIDE)
- BMBF
- ERC [311477]
- Alexander von Humboldt foundation
- German National Academic Foundation
- Human Frontier Science Program Long-term Fellowship
- ETH Zurich Postdoctoral Fellowship
- European Research Council (ERC) [311477] Funding Source: European Research Council (ERC)
PoyD is a radical S-adenosyl methionine epimerase that introduces multiple D-configured amino acids at alternating positions into the highly complex marine peptides polytheonamide A and B. This novel post-translational modification contributes to the ability of the polytheonamides to form unimolecular minimalistic ion channels and its cytotoxic activity at picomolar levels. Using a genome mining approach we have identified additional PoyD homologues in various bacteria. Three enzymes were expressed in E. coli with their cognate as well as engineered peptide precursors and shown to introduce diverse D-amino acid patterns into all-l peptides. The data reveal a family of architecturally and functionally distinct enzymes that exhibit high regioselectivity, substrate promiscuity, and irreversible action and thus provide attractive opportunities for peptide engineering.
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