期刊
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
卷 61, 期 41, 页码 -出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202208361
关键词
Atropisomerism; Cytochrome P450 Monooxygenase; Genome Mining; RiPPs; Stereoisomerism
资金
- LOEWE Center for Translational Biodiversity Genomics (LOEWE TBG)
- Funds of the Chemical Industry Germany
- Kekule Fellowship of the Funds of the Chemical Industry Germany
- Projekt DEAL
This study discovered a new family of ribosomally synthesized and posttranslationally modified peptides, named atropopeptides. The characterization of two atropopeptide biosynthetic pathways revealed a two-step maturation process. Atropopeptides promote pro-angiogenic cell functions.
Biomacromolecules are known to feature complex three-dimensional shapes that are essential for their function. Among natural products, ambiguous molecular shapes are a rare phenomenon. The hexapeptide tryptorubin A can adopt one of two unusual atropisomeric configurations. Initially hypothesized to be a non-ribosomal peptide, we show that tryptorubin A is the first characterized member of a new family of ribosomally synthesized and posttranslationally modified peptides (RiPPs) that we named atropopeptides. The sole modifying enzyme encoded in the gene cluster, a cytochrome P450 monooxygenase, is responsible for the atropospecific formation of one carbon-carbon and two carbon-nitrogen bonds. The characterization of two additional atropopeptide biosynthetic pathways revealed a two-step maturation process. Atropopeptides promote pro-angiogenic cell functions as indicated by an increase in endothelial cell proliferation and undirected migration. Our study expands the biochemical space of RiPP-modifying enzymes and paves the way towards the chemoenzymatic utilization of atropopeptide-modifying P450s.
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