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Publication Abstract from PubMed

The involvement of low-molecular-weight thiols in the biosynthesis of natural products is rarely reported. During lincomycin A biosynthesis, ergothioneine (EGT) is incorporated in the S-glycosylation catalyzed by LmbT. In contrast to the widely reported glycosylation of nitrogen and oxygen atoms, the glycosylation of sulfur atoms is less studied. In particular, the crystal structure of enzymes that glycosylate thiols on small molecules rather than peptides has not been reported. Here, we report the crystal structures of LmbT in apo form and in complex with GDP and EGT S-conjugated lincosamine. We found that LmbT has a characteristic glycosyltransferase type B fold, which forms a symmetric homotetramer. The substrates are bound deeply in the catalytic cleft. Consistent with the substrate structure, LmbT does not have the large peptide binding groove of the previously reported S-glycosyltransferase. Combined with site-directed mutagenesis, we propose a catalytic mechanism for the unusual EGT-mediated S-glycosylation in natural product biosynthesis.

Structural Basis of Low-Molecular-Weight Thiol Glycosylation in Lincomycin A Biosynthesis.,Dai Y, Cheng Y, Ding W, Qiao H, Zhang D, Zhong G, Xia M, Tao J, Sun P, Fang P, Liu W ACS Chem Biol. 2023 Jun 16;18(6):1271-1277. doi: 10.1021/acschembio.3c00185. Epub , 2023 Jun 5. PMID:37272735^[1]

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