Engineered geranyl diphosphate methyltransferase produces 2-methyl-dimethylallyl diphosphate as a noncanonical C 6 unit for terpenoid biosynthesis.

Autor: Xia CY; Hubei Key Laboratory of Cell Homeostasis, College of Life Science, Wuhan University, Wuhan, China., Lu BW; Hubei Key Laboratory of Cell Homeostasis, College of Life Science, Wuhan University, Wuhan, China., Cui JY; Hubei Key Laboratory of Cell Homeostasis, College of Life Science, Wuhan University, Wuhan, China., Wang BY; Hubei Key Laboratory of Cell Homeostasis, College of Life Science, Wuhan University, Wuhan, China., Sun YY; Hubei Key Laboratory of Cell Homeostasis, College of Life Science, Wuhan University, Wuhan, China., Gan F; Hubei Key Laboratory of Cell Homeostasis, College of Life Science, Wuhan University, Wuhan, China.; TaiKang Center for Life and Medical Science, Wuhan University, Wuhan, China.; Hubei Provincial Cooperative Innovation Center of Industrial Fermentation, Wuhan, China.
Jazyk: angličtina
Zdroj: Synthetic and systems biotechnology [Synth Syst Biotechnol] 2022 Dec 19; Vol. 8 (1), pp. 107-113. Date of Electronic Publication: 2022 Dec 19 (Print Publication: 2023).
DOI: 10.1016/j.synbio.2022.12.002
Abstrakt: Terpenoids constitute the largest class of natural products with complex structures, essential functions, and versatile applications. Creation of new building blocks beyond the conventional five-carbon (C 5 ) units, dimethylallyl diphosphate (DMAPP) and isopentenyl diphosphate, expands significantly the chemical space of terpenoids. Structure-guided engineering of an S -adenosylmethionine-dependent geranyl diphosphate (GPP) C2-methyltransferase from Streptomyces coelicolor yielded variants converting DMAPP to a new C 6 unit, 2-methyl-DMAPP. Mutation of the Gly residue at the position 202 resulted in a smaller substrate-binding pocket to fit DMAPP instead of its native substrate GPP. Replacement of Phe residue at the position 222 with a Tyr residue contributed to DMAPP binding via hydrogen bond. Furthermore, using Escherichia coli as the chassis, we demonstrated that 2-methyl-DMAPP was accepted as a start unit to generate noncanonical trans - and cis -prenyl diphosphates (C 5n+1 ) and terpenoids. This work provides insights into substrate recognition of prenyl diphosphate methyltransferases, and strategies to diversify terpenoids by expanding the building block portfolio.
Competing Interests: We have no conflict of interest to declare.
(© 2022 The Authors.)
Databáze: MEDLINE
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