8X3Y
ThDP-dependent HKA synthase
Summary for 8X3Y
| Entry DOI | 10.2210/pdb8x3y/pdb |
| Descriptor | BbmA, ADENOSINE-5'-DIPHOSPHATE, THIAMINE DIPHOSPHATE, ... (5 entities in total) |
| Functional Keywords | thdp-dependent hka synthase, biosynthetic protein |
| Biological source | Brevibacillus |
| Total number of polymer chains | 2 |
| Total formula weight | 126524.99 |
| Authors | |
| Primary citation | Liu, T.,Wang, G.,Yu, J.,Li, M.,Peng, T.,Wang, J.,Li, H.,Su, X.D.,Jiang, C.,Ye, M.,Yang, D.,Ma, M. Structural insights into two thiamine diphosphate-dependent enzymes and their synthetic applications in carbon-carbon linkage reactions. Nat.Chem., 2025 Cited by PubMed Abstract: The α-hydroxy-β-keto acid synthases are thiamine diphosphate-dependent enzymes catalysing carbon-carbon linkage reactions in the biosynthesis of primary metabolites and various secondary metabolites. However, the substrate selectivity and catalytic stereoselectivity of α-hydroxy-β-keto acid synthases are poorly understood, greatly hindering their synthetic application in generating diverse carbon frameworks. We here report the discovery of two new α-hydroxy-β-keto acid synthases CsmA and BbmA, which show different substrate selectivities in catalysing carbon-carbon coupling reactions between two β-keto acids. Four crystal structures of CsmA or BbmA complexed with thiamine diphosphate and their substrates were determined, clearly revealing their structural bases of substrate selectivity and catalytic stereoselectivity. Substrate scope expansion enables us to generate 120 α-hydroxy-β-keto acids together with 240 NaBH-reduction products. Furthermore, we applied CsmA and BbmA into enzymatic total synthesis, generating 36 γ-butyrolactone-containing furanolides. These results provide new structural insights into the catalyses of α-hydroxy-β-keto acid synthases and highlight their great potential in carboligation catalysis and synthetic applications. PubMed: 40369129DOI: 10.1038/s41557-025-01822-y PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.15 Å) |
Structure validation
Download full validation report
