Biosynthetic Gene Cluster of a d‐Tryptophan‐Containing Lasso Peptide, MS‐271

MS‐271, produced by Streptomyces sp. M‐271, is a lasso peptide natural product comprising 21 amino acid residues with a d‐tryptophan at its C terminus. Because lasso peptides are ribosomal peptides, the biosynthesis of MS‐271, especially the mechanism of d‐Trp introduction, is of great interest. The...

Full description

Saved in:
Bibliographic Details
Published in:Chembiochem : a European journal of chemical biology 2018-10, Vol.19 (19), p.2045-2048
Main Authors: Feng, Zhi, Ogasawara, Yasushi, Nomura, Satoshi, Dairi, Tohru
Format: Article
Language:English
Subjects:
Amino acids
antibiotics
Biosynthesis
Cysteine proteinase
d-amino acids
Enzymes
Epimerase
epimerases
Gene deletion
Gene expression
Gene sequencing
Genes
Genomes
lasso peptides
Natural products
Peptides
Precursors
Proteins
Residues
Streptomyces
Tryptophan
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:MS‐271, produced by Streptomyces sp. M‐271, is a lasso peptide natural product comprising 21 amino acid residues with a d‐tryptophan at its C terminus. Because lasso peptides are ribosomal peptides, the biosynthesis of MS‐271, especially the mechanism of d‐Trp introduction, is of great interest. The MS‐271 biosynthetic gene cluster was identified by draft genome sequencing of the MS‐271 producer, and it was revealed that the precursor peptide contains all 21 amino acid residues including the C‐terminal tryptophan. This suggested that the d‐Trp residue is introduced by epimerization. Genes for modification enzymes such as a macrolactam synthetase (mslC), precursor peptide recognition element (mslB1), cysteine protease (mslB2), disulfide oxidoreductases (mslE, mslF), and a protein of unknown function (mslH) were found in the flanking region of the precursor peptide gene. Although obvious epimerase genes were absent in the cluster, heterologous expression of the putative MS‐271 cluster in Streptomyces lividans showed that it contains all the necessary genes for MS‐271 production including a gene for a new peptide epimerase. Furthermore, a gene‐deletion experiment indicated that MslB1, ‐B2, ‐C and ‐H were indispensable for MS‐271 production and that some interactions of the biosynthetic enzymes were essential for the biosynthesis of MS‐271. Roping in an epimerase: The biosynthetic gene cluster of the d‐tryptophan‐containing lasso peptide MS‐271 of Streptomyces sp. M‐271 has been identified. The participation of a new peptide epimerase in MS‐271 biosynthesis was postulated by sequence analysis and heterologous expression of the gene cluster.
ISSN:1439-4227
1439-7633
DOI:10.1002/cbic.201800315