9uuv | pdb_00009uuv
beta barrel protein-LucK
Structural highlights
Publication Abstract from PubMedLucensimycin 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 luc biosynthetic gene cluster from Streptomyces fagopyri 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 horizontal line rather than a pericyclic reaction horizontal line 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 beta-barrel enzymes in polyketide biosynthesis. Enzymatic Stereoselective Nucleophilic Cyclization Governs Atypical Spirotetronate Assembly in Lucensimycin A Biosynthesis.,Xi MY, Zhang B, Peng T, Ma XX, Zhu A, Wang ZJ, Gu Y, Tan RX, Ge HM J Am Chem Soc. 2025 Jul 9;147(27):24077-24084. doi: 10.1021/jacs.5c07754. Epub , 2025 Jun 26. PMID:40569275[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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