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8ftv

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SgvM methyltransferase triple variant (M144V/F329V/T331A) with SAH and 2-oxo-4-phenylbutanoic acid

Structural highlights

8ftv is a 1 chain structure with sequence from Streptomyces griseoviridis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.04Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

R9UTR3_STRGD

Publication Abstract from PubMed

Catalytic asymmetric alpha-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 alpha-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 alpha-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.

A biocatalytic platform for asymmetric alkylation of alpha-keto acids by mining and engineering of methyltransferases.,Ju S, Kuzelka KP, Guo R, Krohn-Hansen B, Wu J, Nair SK, Yang Y Nat Commun. 2023 Sep 14;14(1):5704. doi: 10.1038/s41467-023-40980-w. PMID:37709735^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Ju S, Kuzelka KP, Guo R, Krohn-Hansen B, Wu J, Nair SK, Yang Y. A biocatalytic platform for asymmetric alkylation of α-keto acids by mining and engineering of methyltransferases. Nat Commun. 2023 Sep 14;14(1):5704. PMID:37709735 doi:10.1038/s41467-023-40980-w