Natural products containing benzoheterocyclic skeletons are widely found in plants and exhibit various pharmacological activities. To address the current limited availability of these compounds, we herein demonstrate the production of benzopyran, furanocoumarins, and pyranocoumarins in Streptomyces xiamenensis by employing prenyltransferases and two substrate-promiscuous enzymes, XimD and XimE. To avoid the degradation in S. xiamenensis, furanocoumarins and pyranocoumarins were also successfully produced in Escherichia coli. The production of linear furanocoumarins (marmesin) and angular pyranocoumarins (decursinol) reached 3.6 and 3.7 mg/L in shake flasks, respectively. To the best of our knowledge, this is the first report of the microbial production of the plant metabolites furanocoumarins and pyranocoumarins. Our study complements the missing link in the biosynthesis of pyranocoumarins by leveraging the catalytic promiscuity of microbial enzymes.

中文翻译：

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构建用于生产苯并杂环衍生物的微生物宿主。

含有苯并杂环骨架的天然产物广泛存在于植物中并表现出多种药理活性。为了解决这些化合物目前有限的可用性，我们在此证明了通过使用异戊二烯基转移酶和两种底物混杂酶 XimD 和 XimE在厦门链霉菌中生产苯并吡喃、呋喃香豆素和吡喃香豆素。为避免在S. xiamenensis中的降解，在大肠杆菌中也成功地生产了呋喃香豆素和吡喃香豆素。. 摇瓶中线性呋喃香豆素 (marmesin) 和角形吡喃香豆素 (decursinol) 的产量分别达到 3.6 和 3.7 mg/L。据我们所知，这是植物代谢产物呋喃香豆素和吡喃香豆素的微生物生产的第一份报告。我们的研究通过利用微生物酶的催化混杂性来补充吡喃香豆素生物合成中缺失的环节。