Mechanistic Investigations into the Catalytic Mode of a Dehydratase Complex Involved in the Biosynthesis of Lantibiotic Cacaoidin
作者机构：State Key Laboratory of Bioorganic and Natural Products ChemistryShanghai Institute of Organic ChemistryUniversity of Chinese Academy of Sciences345 Lingling RoadShanghai200032 China School of Chemistry and Materials ScienceHangzhou Institute for Advanced StudyUniversity of Chinese Academy of Sciences1 Sublane XiangshanHangzhouZhejiang310024 China
出 版 物：《Chinese Journal of Chemistry》 (中国化学（英文版）)
年 卷 期：2023年第41卷第24期
页 面：3579-3586页
核心收录：
学科分类：07[理学] 070303[理学-有机化学] 0703[理学-化学]
基 金：supported in part by grants from the National Key Research and Development Program of China(2022YFC2303100 for L.P and W.L) the National Natural Science Foundation of China(32030002 and 22193070 for W.L) the Science and Technology Commission of Shanghai Municipality(20XD1425200 for L.P) the CAS Youth Interdisciplinary Team(JCTD-2022-10 for L.P).
主 题：Ribosomally synthesized and post-translationally modified peptide Antibiotics Enzyme models Natural products Dehydratase complex Cacaoidin Dehydration reaction
摘 要：Dehydration of serine/threonine residues necessitates the activity of a dehydratase enzyme(domain)during the biosynthesis of RiPP.Recently,it was reported that dehydration in the thioviridamide pathway relies on a distinct dehydratase complex that showcases the activities of a phosphotransferase TvaC for serine/threonine phosphorylation and a lyase TvaD for subsequent phosphate elimination.Herein,we report that dehydration reactions in the pathway 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 in a directional manner from the C-terminus of the core peptide(CP)to the 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 in a manner independently of LP.This work advances our understanding of the dehydration process during cacaoidin formation,and provides useful enzymes and methods for the studies of the rapidly emerging RiPPs.
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