Reaction: (1) pantetheine + (3S,5S)-carbapenam-3-carboxylate + S-adenosyl-L-methionine = (2R,3R,5S)-2-(S-pantetheinyl)-carbapenam-3-carboxylate + 5′-deoxyadenosine + L-methionine
(2) pantetheine + (5R)-carbapen-2-em-3-carboxylate + S-adenosyl-L-methionine = 6-desethyl-OA-6129 A + 5′-deoxyadenosine + L-methionine
Glossary: 6-desethyl-OA-6129 A = (5S)-3-[({2-[(2R)-2,4-dihydroxy-3,3-dimethylbutanamido]propanamido}ethyl)sulfanyl]-7-oxo-1-azabicyclo[3.2.0]oct-2-ene-2-carboxylate
Other name(s): thnL (gene name)
Systematic name: (2R,3R,5S)-2-(S-pantetheinyl)-carbapenam-3-carboxylate lyase
Comments: The enzyme uses radical SAM (AdoMet) chemistry to catalyse thioether bond formation between pantetheine and C-2 of the carbapenam precursors (3S,5S)-carbapenam-3-carboxylate or (5R)-carbapen-2-em-3-carboxylate, leading to formation of complex carbapenems. Contains a bound [4Fe-4S] cluster and hydroxocobalamin.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Sinner, E.K., Li, R., Marous, D.R. and Townsend, C.A. ThnL, a B12-dependent radical S-adenosylmethionine enzyme, catalyzes thioether bond formation in carbapenem biosynthesis. Proc. Natl. Acad. Sci. USA 119 (2022) e2206494119. [PMID: 35969793]