8ki5

PhmA, a type I diterpene synthase without NST/DTE motif

spinqualitylabelsall models 8ki5, resolution 2.01Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8ki5 is a 1 chain structure with sequence from Phoma. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.01Å Ligands: FOH Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Phomactin diterpenoids possess a unique bicyclo[9.3.1]pentadecane skeleton with multiple oxidative modifications, and are good platelet-activating factor (PAF) antagonists that can inhibit PAF-induced platelet aggregation. In this study, we identified the gene cluster (phm) responsible for the biosynthesis of phomactins from a marine fungus, Phoma sp. ATCC 74077. Despite the complexity of their structures, phomactin biosynthesis only requires two enzymes: a type I diterpene cyclase PhmA and a P450 monooxygenase PhmC. PhmA was found to catalyze the formation of the phomactatriene, while PhmC sequentially catalyzes the oxidation of multiple sites, leading to the generation of structurally diverse phomactins. The rearrangement mechanism of the diterpene scaffold was investigated through isotope labeling experiments. Additionally, we obtained the crystal complex of PhmA with its substrate analogue FGGPP and elucidated the novel metal-ion-binding mode and enzymatic mechanism of PhmA through site-directed mutagenesis. This study provides the first insight into the biosynthesis of phomactins, laying the foundation for the efficient production of phomactin natural products using synthetic biology approaches. Biosynthesis of Phomactin Platelet Activating Factor Antagonist Requires a Two-Enzyme Cascade.,Zhang L, Zhang B, Zhu A, Liu SH, Wu R, Zhang X, Xu Z, Tan RX, Ge HM Angew Chem Int Ed Engl. 2023 Nov 20;62(47):e202312996. doi: , 10.1002/anie.202312996. Epub 2023 Oct 19. PMID:37804495 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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