Crystal Structure of the Ergothioneine Sulfoxide Synthase from Candidatus Chloracidobacterium thermophilum and Structure-Guided Engineering To Modulate Its Substrate Selectivity.

ABSTRACT: Ergothioneine is a thiohistidine derivative with potential benefits on many aging-related diseases. The central step of aerobic ergothioneine biosynthesis is the oxidative C-S bond formation reaction catalyzed by mononuclear nonheme iron sulfoxide synthases (EgtB and Egt1). Thus far, only the Mycobacterium thermoresistibile EgtB (EgtB Mth ) crystal structure is available, while the structural information for the more industrially attractive Egt1 enzyme is not. Herein, we reported the crystal structure of the ergothioneine sulfoxide synthase (EgtB Cth ) from Candidatus Chloracidobacterium thermophilum. EgtB Cth has both EgtB- and Egt1-type of activities. Guided by the structural information, we conducted Rosetta Enzyme Design calculations, and we biochemically demonstrated that EgtB Cth can be engineered more toward Egt1-type of activity. This study provides information regarding the factors governing the substrate selectivity in Egt1- and EgtB-catalysis and lays the groundwork for future sulfoxide synthase engineering toward the development of an effective ergothioneine process through a synthetic biology approach.

SUBMITTER: Naowarojna N 

PROVIDER: S-EPMC7133768 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature