Unprecedented Noncanonical Features of the Nonlinear Nonribosomal Peptide Synthetase Assembly Line for WS9326A Biosynthesis

Myoun Su Kim, Munhyung Bae, Ye Eun Jung, Jung Min Kim, Sunghoon Hwang, Myoung Chong Song, Yeon Hee Ban, Eun Seo Bae, Suckchang Hong, Sang Kook Lee, Sun Shin Cha, Dong Chan Oh, Yeo Joon Yoon

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Systematic inactivation of nonribosomal peptide synthetase (NRPS) domains and translocation of the thioesterase (TE) domain revealed several unprecedented nonlinear NRPS assembly processes during the biosynthesis of the cyclodepsipeptide WS9326A in Streptomyces sp. SNM55. First, two sets of type ΙΙ TE (TEΙΙ)-like enzymes mediate the shuttling of activated amino acids between two sets of stand-alone adenylation (A)-thiolation (T) didomain modules and an “A-less” condensation (C)-T module with distinctive specificities and flexibilities. This was confirmed by the elucidation of the affinities of the A-T didomains for the TEΙΙs and its structure. Second, the C-T didomain module operates iteratively and independently from other modules in the same protein to catalyze two chain elongation cycles. Third, this biosynthetic pathway includes the first example of module skipping, where the interpolated C and T domains are required for chain transfer.

Original languageEnglish
Pages (from-to)19766-19773
Number of pages8
JournalAngewandte Chemie - International Edition
Volume60
Issue number36
DOIs
StatePublished - 1 Sep 2021

Keywords

  • biosynthesis
  • module iteration
  • module skipping
  • nonribosomal peptide synthetase
  • shuttling thioesterase

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