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Updated: Jun 12, 2026

Visualization of Bacterial Resistance using Fluorescent Antibiotic Probes
Published on: March 2, 2020
An ATP-independent strategy for amide bond formation in antibiotic biosynthesis
Masanori Funabashi1, Zhaoyong Yang, Koichi Nonaka
1Bioengineering Research Group I, Process Technology Research Laboratories, Daiichi Sankyo Co., Ltd., Fukushima, Japan.
Abstract:
A-503083 B, a capuramycin-type antibiotic, contains an L-aminocaprolactam and an unsaturated hexuronic acid that are linked via an amide bond. A putative class C beta-lactamase (CapW) was identified within the biosynthetic gene cluster that-in contrast to the expected beta-lactamase activity-catalyzed an amide-ester exchange reaction to eliminate the L-aminocaprolactam with concomitant generation of a small but significant amount of the glyceryl ester derivative of A-503083 B, suggesting a potential role for an ester intermediate in the biosynthesis of capuramycins. A carboxyl methyltransferase, CapS, was subsequently demonstrated to function as an S-adenosylmethionine-dependent carboxyl methyltransferase to form the methyl ester derivative of A-503083 B. In the presence of free L-aminocaprolactam, CapW efficiently converts the methyl ester to A-503083 B, thereby generating a new amide bond. This ATP-independent amide bond formation using methyl esterification followed by an ester-amide exchange reaction represents an alternative to known strategies of amide bond formation.
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