9BWL
Crystal structure of polyketoacyl-CoA thiolase from Burkholderia sp in complex with butyryl-coA
This is a non-PDB format compatible entry.
Summary for 9BWL
| Entry DOI | 10.2210/pdb9bwl/pdb |
| Related | 9BWK |
| Descriptor | Acetyl-CoA acetyltransferase, COENZYME A (3 entities in total) |
| Functional Keywords | thiolases biosynthetic thiolases type iii polyketide synthase, lyase |
| Biological source | Burkholderia sp. RF2-non_BP3 |
| Total number of polymer chains | 2 |
| Total formula weight | 84419.47 |
| Authors | Pereira, J.H.,Wang, Z.,Keasling, J.D.,Adams, P.D. (deposition date: 2024-05-21, release date: 2025-08-27, Last modification date: 2025-12-24) |
| Primary citation | Wang, Z.,Cheong, S.,Pereira, J.H.,Hu, W.,Guo, Y.,DeGiovanni, A.,Lan, G.,Kim, J.,Haushalter, R.W.,Lee, T.S.,Adams, P.D.,Keasling, J.D. A highly active Burkholderia polyketoacyl-CoA thiolase for production of triacetic acid lactone. Nat Commun, 16:10990-10990, 2025 Cited by PubMed Abstract: Triacetic acid lactone (TAL) is a versatile platform chemical traditionally biosynthesized via decarboxylative Claisen condensation by 2-pyrone synthase. However, this route is limited by poor efficiency and dependence on malonyl-CoA. Here, we show that non-decarboxylative Claisen condensation by polyketoacyl-CoA thiolases offers a more efficient alternative. Through mining homologs of a previously reported enzyme from Cupriavidus necator, we identify five thiolases with TAL production activity. One candidate, BktBbr from Burkholderia sp. RF2-non_BP3, exhibits approximately 30-fold higher activity in vitro and supports 30-fold higher TAL titers in Escherichia coli compared to the original enzyme. Fed-batch fermentation achieves titers up to 2.8 g L⁻¹. Structural analysis of BktBbr co-crystallized with CoA esters guides rational engineering to further enhance performance. Our discovery of a highly active thiolase establishes an alternative enzymatic route to produce TAL efficiently, providing a scalable foundation for sustainable biomanufacturing. PubMed: 41365852DOI: 10.1038/s41467-025-65946-y PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.1 Å) |
Structure validation
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