Download MendeleyA biocatalytic platform for asymmetric alkylation of alpha-keto acids by mining and engineering of methyltransferases
Ju, S., Kuzelka, K.P., Guo, R., Krohn-Hansen, B., Wu, J., Nair, S.K., Yang, Y.(2023) Nat Commun 14: 5704-5704
- PubMed: 37709735
- DOI: https://doi.org/10.1038/s41467-023-40980-w
- Primary Citation of Related Structures:
8FTR, 8FTS, 8FTV - PubMed Abstract:
Catalytic asymmetric α-alkylation of carbonyl compounds represents a long-standing challenge in synthetic organic chemistry. Herein, we advance a dual biocatalytic platform for the efficient asymmetric alkylation of α-keto acids. First, guided by our recently obtained crystal structures, we develop SgvM VAV as a general biocatalyst for the enantioselective methylation, ethylation, allylation and propargylation of a range of α-keto acids with total turnover numbers (TTNs) up to 4,600. Second, we mine a family of bacterial HMTs from Pseudomonas species sharing less than 50% sequence identities with known HMTs and evaluated their activities in SAM regeneration. Our best performing HMT from P. aeruginosa, PaHMT, displays the highest SAM regeneration efficiencies (TTN up to 7,700) among HMTs characterized to date. Together, the synergistic use of SgvM VAV and PaHMT affords a fully biocatalytic protocol for asymmetric methylation featuring a record turnover efficiency, providing a solution to the notorious problem of asymmetric alkylation.
Organizational Affiliation:
Department of Chemistry and Biochemistry, University of California, Santa Barbara, CA, USA.
