Aminoacyl chain translocation catalysed by a type II thioesterase domain in an unusual non-ribosomal peptide synthetase

Shan Wang, William D.G. Brittain, Qian Zhang, Zhou Lu, Ming Him Tong, Kewen Wu, Kwaku Kyeremeh, Matthew Jenner* (Corresponding Author), Yi Yu* (Corresponding Author), Steven L. Cobb* (Corresponding Author), Hai Deng*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Non-Ribosomal Peptide Synthetases (NRPSs) assemble a diverse range of natural products with important applications in both medicine and agriculture. They consist of several multienzyme subunits that must interact with each other in a highly controlled manner to facilitate efficient chain transfer, thus ensuring biosynthetic fidelity. Several mechanisms for chain transfer are known for NRPSs, promoting structural diversity. Herein, we report the first biochemically characterized example of a type II thioesterase (TEII) domain capable of catalysing aminoacyl chain transfer between thiolation (T) domains on two separate NRPS subunits responsible for installation of a dehydrobutyrine moiety. Biochemical dissection of this process reveals the central role of the TEII-catalysed chain translocation event and expands the enzymatic scope of TEII domains beyond canonical (amino)acyl chain hydrolysis. The apparent co-evolution of the TEII domain with the NRPS subunits highlights a unique feature of this enzymatic cassette, which will undoubtedly find utility in biosynthetic engineering efforts.

Original languageEnglish
Article number62
Number of pages14
JournalNature Communications
Volume13
Issue number1
Early online date10 Jan 2022
DOIs
Publication statusPublished - 10 Jan 2022

Keywords

  • Biosynthesis
  • Enzyme mechanisms
  • Enzymes

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