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Mechanistic Investigations into the Catalytic Mode of a Dehydratase Complex Involved in the Biosynthesis of Lantibiotic Cacaoidin
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  • Yanqing Xue,
  • Miao Li,
  • Ling Hu,
  • Jianing Liu,
  • Lifeng Pan,
  • Wen Liu
Yanqing Xue
Shanghai Institute of Organic Chemistry Chinese Academy of Sciences
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Miao Li
Shanghai Institute of Organic Chemistry Chinese Academy of Sciences
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Ling Hu
Shanghai Institute of Organic Chemistry Chinese Academy of Sciences
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Jianing Liu
Shanghai Institute of Organic Chemistry Chinese Academy of Sciences
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Lifeng Pan
Shanghai Institute of Organic Chemistry
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Wen Liu
Shanghai Institute of Organic Chemistry Chinese Academy of Sciences

Corresponding Author:wliu@sioc.ac.cn

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Abstract

Dehydration of serine/threonine residues necessitates the activity of a dehydratase enzyme (domain) during the biosynthesis of ribosomally synthesized and post-translationally modified peptide (RiPP). Recently, it was reported that the dehydration process in thioviridamide relies on a distinct dehydratase complex which showcases the activities of a phosphotransferase TvaC for serine/threonine phosphorylation and a lyase TvaD for subsequent phosphate elimination. Herein, we report that the dehydration process of lantibiotic cacaoidin involves a similar dehydratase complex, CaoK/CaoY. Remarkably, this dehydratase complex exhibits flexible enzymatic activity and tolerates significant variations in its substrate peptide sequence. By binding with the leader peptide (LP) sequence of precursor peptide CaoA, the dehydration reactions proceed directionality from the C-terminus of the core peptide (CP) to its N-terminus, and C-terminally truncated variants of CP are acceptable. We show that fusing CaoK to CaoY in a 1:1 molar ratio enables the resulting enzyme CaoYK to exert enhanced dehydration activity. CaoK binds with the LP to improve its own solubility and to ensure the phosphate transfer activity, while CaoY functions independently of the LP. This work advances our understanding of the dehydration process of cacaoidin, and provides valuable enzymes and methods for the studies of the rapidly emerging RiPPs.
23 Jul 2023Reviewer(s) Assigned
15 Aug 2023Review(s) Completed, Editorial Evaluation Pending
15 Aug 2023Editorial Decision: Revise Minor
01 Sep 20231st Revision Received
04 Sep 2023Review(s) Completed, Editorial Evaluation Pending
04 Sep 2023Submission Checks Completed
04 Sep 2023Assigned to Editor
04 Sep 2023Editorial Decision: Accept