A biotechnological approach toward the plant metabolite and regulator cis‐(+)‐12‐oxophytodienoic acid (cis‐(+)‐12‐OPDA) in a one‐pot process with >99% conversion, at least 90% selectivity and ≤10% of side products as well as a high diastereoselectivity (leading to d.r. of at least 90:10) is reported. The optimized organic‐synthetic enzyme cascade for preparing this bioactive and commercial molecule with pharmaceutical relevance on a gram per L scale is designed based on its biosynthetic pathway starting from cheap and readily accessible linolenic acid. Toward this end, a recombinant biocatalyst system has been prepared for carrying out the most critical two key steps in a tailored manner, thus avoiding sensitive intermediate decomposition. Furthermore, cis‐(+)‐12‐OPDA is successfully modified via a cross‐alkene metathesis reaction with conversions of up to >99%, leading to a compound library of new cis‐(+)‐12‐OPDA derivatives with different substitution pattern of the side chain at the 2‐position. By means of such a combined biotechnological and chemocatalytic route, a straightforward approach to a structurally unique oxylipin library is realized, which would be highly difficult or not accessible by pure chemical and biotechnological methods, respectively.

中文翻译：

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从生物合成途径到生物催化过程和化学催化修饰：三步酶促级联反应到植物代谢物顺式（+）-12-OPDA和易位产物。

一种生物技术方法，以一锅法处理植物代谢产物和调节剂顺式（+）-12-氧代乙二酸（顺式（+）-12-OPDA）（转化率> 99％，选择性至少90％，且≤10报告了副产物的百分比以及非对映选择性高（导致dr至少为90:10）。优化的有机合成酶级联反应是基于其生物合成途径从廉价且容易获得的亚麻酸开始制备的，该级联反应可制备具有药物相关性（每克克克级）的生物活性和商业分子。为此，已经准备了重组生物催化剂系统，用于以定制的方式执行最关键的两个关键步骤，从而避免了敏感的中间分解。此外，顺式‐（+）‐ 12‐OPDA通过跨烯烃复分解反应成功进行了修饰，转化率高达99％以上，从而形成了具有不同取代模式的新cis ‐（+）‐ 12‐OPDA衍生物的化合物库在2位的侧链。通过这种结合的生物技术和化学催化途径，实现了一种结构独特的脂蛋白文库的直接方法，这将是非常困难的，或者分别通过纯化学和生物技术方法是很难获得的。