Institute for Organic Chemistry and BMWZ Leibniz University of Hannover Schneiderberg 38, 30167, Hannover, Germany.
Chem Commun (Camb). 2020 Sep 21;56(74):10934-10937. doi: 10.1039/d0cc03203d. Epub 2020 Aug 13.
Sorbicillinoids are a large family of fungal secondary metabolites with a diverse range of structures and numerous bioactivites, some of which have pharmaceutical potential. The flavin-dependent monooxygenase SorD from Penicillium chrysogenum (PcSorD) utilizes sorbicillinol to catalyze a broad scope of reactions: formation of oxosorbicillinol and epoxysorbicillinol; intermolecular Diels-Alder and Michael-addition dimerization reactions; and dimerization of a sorbicillinol derivative with oxosorbicillinol. PcSorD shares only 18.3% sequence identity with SorD from Trichoderma reesei (TrSorD) and yet unexpectedly catalyzes many of the same reactions, however, the formation of oxosorbicillinol and bisvertinolone by PcSorD extends the range of reactions catalyzed by a single enzyme. Phylogenetic analysis indicates that PcSorD and TrSorD bind the flavin cofactor covalently but via different residues and point mutations confirm these residues are essential for activity.
索比西菌素类是一类具有多种结构和丰富生物活性的真菌次级代谢产物，其中一些具有药物潜力。青霉（Penicillium chrysogenum）黄素依赖单加氧酶 SorD（PcSorD）利用索比西醇（sorbicillinol）催化广泛的反应：形成氧代索比西醇（oxosorbicillinol）和环氧索比西醇（epoxysorbicillinol）；分子间 Diels-Alder 和 Michael 加成二聚反应；以及索比西醇衍生物与氧代索比西醇的二聚反应。PcSorD 与里氏木霉（Trichoderma reesei）的 SorD 仅共享 18.3%的序列同一性，但出人意料的是，它催化了许多相同的反应，然而，PcSorD 形成氧代索比西醇和双vertinolone 扩展了单个酶催化的反应范围。系统发育分析表明，PcSorD 和 TrSorD 通过不同的残基以共价键结合黄素辅因子，但点突变证实这些残基对活性至关重要。
