9QM2
Crystal Structure of the flavoprotein monooxygenase RslO9 from Streptomyces bottropensis
Summary for 9QM2
| Entry DOI | 10.2210/pdb9qm2/pdb |
| Descriptor | FAD dependent monooxygenase, FLAVIN-ADENINE DINUCLEOTIDE, CHLORIDE ION, ... (4 entities in total) |
| Functional Keywords | monooxygenase, fad-binding, oxidoreductase |
| Biological source | Streptomyces bottropensis |
| Total number of polymer chains | 1 |
| Total formula weight | 60329.72 |
| Authors | Sowa, S.T.,Weddeling, H.G.,Teufel, R. (deposition date: 2025-03-21, release date: 2026-02-11, Last modification date: 2026-02-25) |
| Primary citation | Weddeling, H.G.,Sowa, S.T.,Bialas, E.,Reese, S.,Merten, C.,Lill, M.,Bechthold, A.,Teufel, R. A Hooker Oxygenase Archetype in Polyketide Biosynthesis Challenging the Baeyer-Villiger Monooxygenase Paradigm. J.Am.Chem.Soc., 148:5722-5733, 2026 Cited by PubMed Abstract: Aromatic polyketides from Actinobacteria are structurally complex bioactive natural products with significant therapeutic potential, whose biosynthesis involves polyketide chain assembly, keto reduction, cyclization, and aromatization. This is followed by pathway-specific enzymatic tailoring steps, occasionally including rare oxidative rearrangements of the carbon skeleton, as exemplified by the rishirilides. In this study, we investigate RslO9, a flavin-dependent tailoring key enzyme of rishirilide biosynthesis, previously hypothesized to facilitate a lactone-forming Baeyer-Villiger oxidation of the rishirilide naphthoquinone core and subsequent intramolecular aldol condensation. Through detailed investigation of RslO9's mechanism, structural features, and substrate scope, we unexpectedly found that the naphthoquinone moiety of the non-natural substrate lapachol undergoes hydroxylation followed by a benzilic acid rearrangement, producing the Hooker intermediate-a hallmark of the intricate Hooker oxidation. Our data support a similar alkyl migration mechanism for RslO9's native substrate, upending its prior classification as a Baeyer-Villiger monooxygenase and challenging the proposed role of related enzymes while also providing a novel framework for exploring their catalytic roles. PubMed: 41588612DOI: 10.1021/jacs.5c21759 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.4 Å) |
Structure validation
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