9Z38

Crystal Structure of CalO4 from Micromonospora echinospora

Summary for 9Z38

• Entry DOI: 10.2210/pdb9z38/pdb
• Descriptor: 3-oxoacyl-[acyl-carrier-protein] synthase-3, MAGNESIUM ION, CHLORIDE ION, ... (6 entities in total)
• Functional Keywords: calicheamicin, acyltransferase, thiolase, transferase
• Biological source: Micromonospora echinospora
• Total number of polymer chains: 2
• Total formula weight: 77536.47

Authors

Pang, F.,Townsend, C.A. (deposition date: 2025-11-05, release date: 2026-08-05, Last modification date: 2026-09-02)

Primary citation

Pang, F.,Peng, Y.J.,Thadkapally, S.,Townsend, C.A.
Thioester Bond Formation Catalyzed by CalO4: A beta-Ketoacyl-ACP Synthase III-like Acyltransferase in Calicheamicin Biosynthesis.
Acs Chem.Biol., 2026

PubMed Abstract: β-Ketoacyl-ACP synthase (KAS) III enzymes play central roles in fatty acid biosynthesis and the production of various natural products. While their canonical function involves catalyzing C-C bond formation between acetyl-CoA and malonyl acyl-carrier-proteins (ACPs), an increasing number of non-canonical activities have been reported among KAS III homologues, including C-O and C-N bond formation. Here, we describe a KAS III family enzyme, CalO4, that catalyzes C-S bond formation during the biosynthesis of the potent antitumor agent calicheamicin. We successfully reconstituted its transacylation activities, demonstrated C-S bond formation, and assessed its substrate selectivity. Furthermore, X-ray crystallography combined with molecular docking and mutational analysis identified key residues likely involved in substrate selection and catalysis. This work not only expands the functional diversity of the KAS III family but also provides a potential biocatalyst for hindered C-S bond formation and a target for engineering novel calicheamicin-like or other bioactive compounds.

PubMed: 42616590
DOI: 10.1021/acschembio.6c00389

Experimental method

X-RAY DIFFRACTION (1.64 Å)