Flavonoids are a diverse set of natural products with promising bioactivities including anti-inflammatory, anti-cancer, and neuroprotective properties. Previously, the oleaginous host has been engineered to produce high titers of the base flavonoid naringenin. Here, we leverage this host along with a set of bioconversion strains to produce the flavone apigenin and its glycosylated derivative isovitexin, two potential nutraceutical and pharmaceutical candidates. Through downstream strain selection, co-culture optimization, media composition, and mutant isolation, we were able to produce168 mg/L of apigenin, representing a 46% conversion rate of 2-(R/S)-naringenin to apigenin. This apigenin platform was modularly extended to produce isovitexin by addition of a second bioconversion strain. Together, these results demonstrate the promise of microbial production and modular bioconversion to access diversified flavonoids.

中文翻译：

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利用解脂耶氏酵母柚皮素底盘进行芹菜素和相关葡萄糖苷的生物合成


类黄酮是多种天然产物，具有良好的生物活性，包括抗炎、抗癌和神经保护特性。此前，含油宿主已被改造为可产生高滴度的基础类黄酮柚皮素。在这里，我们利用该宿主和一组生物转化菌株来生产黄酮芹菜素及其糖基化衍生物异牡荆素，这是两种潜在的营养保健品和药物候选物。通过下游菌株选择、共培养优化、培养基组成和突变体分离，我们能够生产 168 mg/L 的芹菜素，即 2-(R/S)-柚皮素到芹菜素的转化率为 46%。通过添加第二个生物转化菌株，该芹菜素平台被模块化扩展以生产异牡荆素。总之，这些结果证明了微生物生产和模块化生物转化获得多样化黄酮类化合物的前景。