6KOG
Ketosynthase domain in tenuazonic acid synthetase 1 (TAS1).
Summary for 6KOG
| Entry DOI | 10.2210/pdb6kog/pdb |
| Descriptor | Hybrid PKS-NRPS synthetase TAS1, GLYCEROL, SULFATE ION, ... (4 entities in total) |
| Functional Keywords | ketosynthase domain, cyclization, tetramic acid ring formation, nrps-pks hybrid enzyme, toxin, biosynthetic protein |
| Biological source | Pyricularia oryzae 70-15 (Rice blast fungus) |
| Total number of polymer chains | 2 |
| Total formula weight | 96223.37 |
| Authors | Yun, C.S.,Nishimoto, K.,Motoyama, T.,Hino, T.,Nagano, S.,Osada, H. (deposition date: 2019-08-10, release date: 2020-07-01, Last modification date: 2023-11-22) |
| Primary citation | Yun, C.S.,Nishimoto, K.,Motoyama, T.,Shimizu, T.,Hino, T.,Dohmae, N.,Nagano, S.,Osada, H. Unique features of the ketosynthase domain in a nonribosomal peptide synthetase-polyketide synthase hybrid enzyme, tenuazonic acid synthetase 1. J.Biol.Chem., 295:11602-11612, 2020 Cited by PubMed Abstract: Many microbial secondary metabolites are produced by multienzyme complexes comprising nonribosomal peptide synthetases (NRPSs) and polyketide synthases (PKSs). The ketosynthase (KS) domains of polyketide synthase normally catalyze the decarboxylative Claisen condensation of acyl and malonyl blocks to extend the polyketide chain. However, the terminal KS domain in tenuazonic acid synthetase 1 (TAS1) from the fungus conducts substrate cyclization. Here, we report on the unique features of the KS domain in TAS1. We observed that this domain is monomeric, not dimeric as is typical for KSs. Analysis of a 1.68-Å resolution crystal structure suggests that the substrate cyclization is triggered via proton abstraction from the active methylene moiety in the substrate by a catalytic His-322 residue. Additionally, we show that TAS1 KS promiscuously accepts aminoacyl substrates and that this promiscuity can be increased by a single amino acid substitution in the substrate-binding pocket of the enzyme. These findings provide insight into a KS domain that accepts the amino acid-containing substrate in an NRPS-PKS hybrid enzyme and provide hints to the substrate cyclization mechanism performed by the KS domain in the biosynthesis of the mycotoxin tenuazonic acid. PubMed: 32565425DOI: 10.1074/jbc.RA120.013105 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.68 Å) |
Structure validation
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