6KXF

The ishigamide ketosynthase/chain length factor

Summary for 6KXF

• Entry DOI: 10.2210/pdb6kxf/pdb
• Descriptor: Ketosynthase, ACP, [(3~{R})-2,2-dimethyl-4-[[3-[2-[[(~{E})-oct-2-enoyl]amino]ethylamino]-3-oxidanylidene-propyl]amino]-3-oxidanyl-4-oxidanylidene-butyl] dihydrogen phosphate, ... (5 entities in total)
• Functional Keywords: polyketide synthase, transferase
• Biological source: Streptomyces sp. MSC090213JE08; More
• Total number of polymer chains: 3
• Total formula weight: 90872.06

Authors

Du, D.,Katsuyama, Y.,Horiuchi, M.,Fushinobu, S.,Chen, A.,Davis, T.,Burkart, M.,Ohnishi, Y. (deposition date: 2019-09-10, release date: 2020-05-06, Last modification date: 2020-07-08)

Primary citation

Du, D.,Katsuyama, Y.,Horiuchi, M.,Fushinobu, S.,Chen, A.,Davis, T.D.,Burkart, M.D.,Ohnishi, Y.
Structural basis for selectivity in a highly reducing type II polyketide synthase.
Nat.Chem.Biol., 16:776-782, 2020

PubMed Abstract: In type II polyketide synthases (PKSs), the ketosynthase-chain length factor (KS-CLF) complex catalyzes polyketide chain elongation with the acyl carrier protein (ACP). Highly reducing type II PKSs, represented by IgaPKS, produce polyene structures instead of the well-known aromatic skeletons. Here, we report the crystal structures of the Iga11-Iga12 (KS-CLF) heterodimer and the covalently cross-linked Iga10=Iga11-Iga12 (ACP=KS-CLF) tripartite complex. The latter structure revealed the molecular basis of the interaction between Iga10 and Iga11-Iga12, which differs from that between the ACP and KS of Escherichia coli fatty acid synthase. Furthermore, the reaction pocket structure and site-directed mutagenesis revealed that the negative charge of Asp 113 of Iga11 prevents further condensation using a β-ketoacyl product as a substrate, which distinguishes IgaPKS from typical type II PKSs. This work will facilitate the future rational design of PKSs.

PubMed: 32367018
DOI: 10.1038/s41589-020-0530-0

Experimental method

X-RAY DIFFRACTION (1.98 Å)