9UUV
beta barrel protein-LucK
Summary for 9UUV
| Entry DOI | 10.2210/pdb9uuv/pdb |
| Descriptor | Allene oxide cyclase barrel-like domain-containing protein (2 entities in total) |
| Functional Keywords | beta barrel protein, nucleophilic subsitution, atypical spirotetronate, biosynthetic protein |
| Biological source | Streptomyces fagopyri |
| Total number of polymer chains | 2 |
| Total formula weight | 37469.81 |
| Authors | |
| Primary citation | Xi, M.Y.,Zhang, B.,Peng, T.,Ma, X.X.,Zhu, A.,Wang, Z.J.,Gu, Y.,Tan, R.X.,Ge, H.M. Enzymatic Stereoselective Nucleophilic Cyclization Governs Atypical Spirotetronate Assembly in Lucensimycin A Biosynthesis. J.Am.Chem.Soc., 147:24077-24084, 2025 Cited by PubMed Abstract: Lucensimycin A is a structurally unique spirotetronate polyketide featuring a rare spiro[tetronate-hydrophenanthrene] tetracyclic core, distinct from the classical spiro[tetronate-cyclohexene] scaffolds formed via intramolecular Diels-Alder (IMDA) cyclizations. Here, we identified and characterized the biosynthetic gene cluster from NAX0062, revealing a divergent biosynthetic logic. The pathway begins with type I PKS assembly of a linear polyketide, followed by tetronate ring formation by a canonical tetronate cassette. A flavin-dependent Diels-Alderase (LucM) then catalyzes an IMDA reaction to form a decalin intermediate. Unusually, the Diels-Alderase homologue LucK catalyzes a stereoselective intramolecular nucleophilic cyclization─rather than a pericyclic reaction─to generate the spiro[tetronate-hydrophenanthrene] core, following acetylation by LucN. Oxidative cleavage of a terminal alkene (by LucO3) completes the pathway. Structural and mutational analysis of LucK revealed that Glu16 and Glu85 function as general acid/base catalysts to drive the nucleophilic cyclization reaction, highlighting LucK as a mechanistically distinct cyclase. This work uncovers a previously unrecognized enzymatic strategy for spirocyclic construction and expands the catalytic repertoire of β-barrel enzymes in polyketide biosynthesis. PubMed: 40569275DOI: 10.1021/jacs.5c07754 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.87 Å) |
Structure validation
Download full validation report
