期刊
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
卷 60, 期 15, 页码 8460-8465出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202015975
关键词
biosynthesis; genome mining; natural products; prenylation; peptides; RiPPs
资金
- NIH [GM122521]
- MOE [R148000258114, R148000271114]
- CarnotPasteur Microbe Sant~
- Skaggs Graduate Research Fellowship
- MOE Research Scholarship
Genome mining was used to identify a novel cyanobactin metabolite tolypamide from the freshwater cyanobacterium Tolypothrix sp., which features an unprecedented post-translational prenylation modification on a threonine residue. The enzyme TolF shows strict selectivity for prenylation of serine or threonine, providing potential as a robust tool for synthetic biology.
Cyanobactins comprise a widespread group of peptide metabolites produced by cyanobacteria that are often diversified by post-translational prenylation. Several enzymes have been identified in cyanobactin biosynthetic pathways that carry out chemically diverse prenylation reactions, representing a resource for the discovery of post-translational alkylating agents. Here, genome mining was used to identify orphan cyanobactin prenyltransferases, leading to the isolation of tolypamide from the freshwater cyanobacterium Tolypothrix sp. The structure of tolypamide was confirmed by spectroscopic methods, degradation, and enzymatic total synthesis. Tolypamide is forward-prenylated on a threonine residue, representing an unprecedented post-translational modification. Biochemical characterization of the cognate enzyme TolF revealed a prenyltransferase with strict selectivity for forward O-prenylation of serine or threonine but with relaxed substrate selectivity for flanking peptide sequences. Since cyanobactin pathways often exhibit exceptionally broad substrate tolerance, these enzymes represent robust tools for synthetic biology.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据