NRPS Protein MarQ Catalyzes Flexible Adenylation and Specific S‑Methylation

Maremycins are a group of structurally diverse 2,5-diketopiperazine natural products featuring a rare amino acid building block, S-methyl-l-cysteine (Me-Cys). Three freestanding nonribosomal peptide synthetase (NRPS) proteins from the maremycins biosynthetic pathway were proposed for the formation o...

Full description

Saved in:
Bibliographic Details
Published in:ACS chemical biology 2018-09, Vol.13 (9), p.2387-2391
Main Authors: Huang, Tingting, Duan, Yingyi, Zou, Yi, Deng, Zixin, Lin, Shuangjun
Format: Article
Language:English
Subjects:
Bacterial Proteins - metabolism
Biosynthetic Pathways
Cysteine - analogs & derivatives
Cysteine - metabolism
Humans
Indoles - metabolism
Methylation
Peptide Synthases - metabolism
Piperazine - metabolism
Streptomyces - metabolism
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:Maremycins are a group of structurally diverse 2,5-diketopiperazine natural products featuring a rare amino acid building block, S-methyl-l-cysteine (Me-Cys). Three freestanding nonribosomal peptide synthetase (NRPS) proteins from the maremycins biosynthetic pathway were proposed for the formation of the 2,5-diketopiperazine scaffold: MarQ, MarM, and MarJ. MarQ displays flexible adenylation activity toward Cys, Me-Cys, Ser, and (S)-2,3-diaminopropanoic acid (DAP) and transfers these substrates to MarJ, which is the discrete peptidyl carrier protein (PCP). MarQ could also activate several other amino acids. The embedded methyltransferase (MT) domain in MarQ specifically catalyzes the thiol methylation of MarJ-tethered Cys. The in vitro reconstitution of MarQ and MarJ further provides clear evidence for the reaction sequence of methylation step on Cys. Our study on MarJ/Q tridomain cassette gains valuable insights into maremycins structure diversity and will be exploited to incorporate Me-Cys into natural products by combinatorial biosynthesis.
ISSN:1554-8929
1554-8937
DOI:10.1021/acschembio.8b00364