{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Sinner EK"],"funding":["HHS | National Institutes of Health","NIAID NIH HHS","NIGMS NIH HHS"],"pagination":["e2206494119"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9407657"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["119(34)"],"pubmed_abstract":["Complex carbapenems are important clinical antibiotics used to treat recalcitrant infections. Their biosynthetic gene clusters contain three essential B<sub>12</sub>-dependent radical <i>S</i>-adenosylmethionine (rSAM) enzymes. The majority of characterized enzymes in this subfamily catalyze methyl transfer, but only one is required to sequentially install all methionine-derived carbons in complex carbapenems. Therefore, it is probable that the other two rSAM enzymes have noncanonical functions. Through a series of fermentation and in vitro experiments, we show that ThnL uses radical SAM chemistry to catalyze thioether bond formation between C2 of a carbapenam precursor and pantetheine, uniting initial bicycle assembly common to all carbapenems with later tailoring events unique to complex"],"journal":["Proceedings of the National Academy of Sciences of the United States of America"],"pubmed_title":["ThnL, a B12-dependent radical <i>S</i>-adenosylmethionine enzyme, catalyzes thioether bond formation in carbapenem biosynthesis."],"pmcid":["PMC9407657"],"funding_grant_id":["GM080189","T32 GM080189","AI121072","R01 AI121072"],"pubmed_authors":["Townsend CA","Sinner EK","Marous DR","Li R"],"additional_accession":[]},"is_claimable":false,"name":"ThnL, a B12-dependent radical <i>S</i>-adenosylmethionine enzyme, catalyzes thioether bond formation in carbapenem biosynthesis.","description":"Complex carbapenems are important clinical antibiotics used to treat recalcitrant infections. Their biosynthetic gene clusters contain three essential B<sub>12</sub>-dependent radical <i>S</i>-adenosylmethionine (rSAM) enzymes. The majority of characterized enzymes in this subfamily catalyze methyl transfer, but only one is required to sequentially install all methionine-derived carbons in complex carbapenems. Therefore, it is probable that the other two rSAM enzymes have noncanonical functions. Through a series of fermentation and in vitro experiments, we show that ThnL uses radical SAM chemistry to catalyze thioether bond formation between C2 of a carbapenam precursor and pantetheine, uniting initial bicycle assembly common to all carbapenems with later tailoring events unique to complex","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Aug","modification":"2025-04-19T13:27:43.522Z","creation":"2025-04-19T13:27:43.522Z"},"accession":"S-EPMC9407657","cross_references":{"pubmed":["35969793"],"doi":["10.1073/pnas.2206494119"]}}