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

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

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


Authors

Shan Wang

Qian Zhang

Zhou Lu

Ming Him Tong

Kewen Wu

Kwaku Kyeremeh

Matthew Jenner

Yi Yu

Hai Deng



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.

Citation

Wang, S., Brittain, W. D., Zhang, Q., Lu, Z., Tong, M. H., Wu, K., Kyeremeh, K., Jenner, M., Yu, Y., Cobb, S. L., & Deng, H. (2022). Aminoacyl chain translocation catalysed by a type II thioesterase domain in an unusual non-ribosomal peptide synthetase. Nature Communications, 13(1), https://doi.org/10.1038/s41467-021-27512-0

Journal Article Type Article
Acceptance Date Nov 18, 2021
Online Publication Date Jan 10, 2022
Publication Date 2022
Deposit Date Feb 16, 2022
Publicly Available Date Feb 16, 2022
Journal Nature Communications
Electronic ISSN 2041-1723
Publisher Nature Research
Peer Reviewed Peer Reviewed
Volume 13
Issue 1
DOI https://doi.org/10.1038/s41467-021-27512-0
Public URL https://durham-repository.worktribe.com/output/1213590

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Publisher Licence URL
http://creativecommons.org/licenses/by/4.0/

Copyright Statement
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.






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