关键词: Ortho-hydroxylation 8-Hydroxyquercetin Biocatalysis Biotransformation FMO Flavonoids Gossypetin Hydroxylation Monooxygenase Recombinant protein Synthetic biology

Mesh : Isoflavones / metabolism chemistry biosynthesis Flavonols / metabolism Flavonoids / metabolism chemistry biosynthesis Hydroxylation Substrate Specificity

来  源:   DOI:10.1038/s41598-024-68513-5   PDF(Pubmed)

Abstract:
Flavin-dependent monooxygenases (FMOs) are a valuable group of biocatalysts that can regioselectively introduce a hydroxy group for the targeted modification of biologically active compounds. Here, we present the fdeE, the FMO from Herbaspirillum seropedicae SmR1 that is a part of the naringenin degradation pathway and is active towards a wide range of flavonoids-flavanones, flavones, isoflavones, and flavonols. Bioinformatics and biochemical analysis revealed a high similarity between the analyzed enzyme and other F8H FMOs what might indicate convergent evolutionary mechanism of flavonoid degradation pathway emergence by microorganism. A simple approach with the manipulation of the reaction environment allowed the stable formation of hydroxylation products, which showed very high reactivity in both in vivo and in vitro assays. This approach resulted in an 8-hydroxyquercetin-gossypetin titer of 0.16 g/L and additionally it is a first report of production of this compound.
摘要:
黄素依赖性单加氧酶(FMO)是一类有价值的生物催化剂,其可以区域选择性地引入羟基用于生物活性化合物的靶向修饰。这里,我们展示了fdeE,TheFMOfromHerbaspirillumseropedicaeSmR1,whichisapartofthenaringeninadmissionpathandisactivetowardawiderangeoffeteroids-flavanones,黄酮,异黄酮,和黄酮醇。生物信息学和生化分析揭示了所分析的酶与其他F8HFMO之间的高度相似性,这可能表明微生物出现类黄酮降解途径的趋同进化机制。通过操纵反应环境的简单方法可以稳定地形成羟基化产物,在体内和体外测定中均显示出非常高的反应性。这种方法导致8-羟基槲皮素-棉素滴度为0.16g/L,此外,这是该化合物生产的第一份报告。
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