Reductase of Mutanobactin Synthetase Triggers Sequential C–C Macrocyclization, C–S Bond Formation, and C–C Bond Cleavage
Min Wang, Zhoujie Xie, Shoubin Tang, Ee Ling Chang, Yue Tang, Zhengyan Guo, Yinglu Cui, Bian Wu, Tao Ye, Yihua Chen
Abstract
Mutanobactins (MUBs) and their congeners that contain a macrocycle and/or a thiazepane ring are lipopeptides from Streptococcus mutans, a major causative agent of dental caries. Here we show that the C-terminal reductase domain of MubD releases the lipohexapeptide intermediates in an aldehyde form, which enables a spontaneous C–C macrocyclization. In the presence of a thiol group, the macrocyclized MUBs can further undergo spontaneous C–S bond formation and C–C bond cleavage to generate diverse MUB congeners.
Topics & Concepts
ChemistryCleavage (geology)Bond cleavageReductaseStereochemistryAldehydePeptide bondEnzymeBiochemistryCatalysisEngineeringGeotechnical engineeringFracture (geology)Microbial Natural Products and BiosynthesisNatural product bioactivities and synthesisGenomics and Phylogenetic Studies