Rational Design of Flavonoid Production Routes Using Combinatorial and Precursor-Directed Biosynthesis.,ACS Synthetic Biology

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Rational Design of Flavonoid Production Routes Using Combinatorial and Precursor-Directed Biosynthesis.
ACS Synthetic Biology ( IF 3.7 ) Pub Date : 2020-06-11 , DOI: 10.1021/acssynbio.0c00172
Johann E Kufs _{1,

2} , Sandra Hoefgen ₁ , Julia Rautschek ₁ , Alexander U Bissell _{1,

2} , Carola Graf ₃ , Jonas Fiedler _{1,

2} , Daniel Braga ₄ , Lars Regestein ₅ , Miriam A Rosenbaum _{2,

5} , Julian Thiele ₃ , Vito Valiante ₁

Affiliation

Combinatorial biosynthesis has great potential for designing synthetic circuits and amplifying the production of new active compounds. Studies on multienzyme cascades are extremely useful for improving our knowledge on enzymatic catalysis. In particular, the elucidation of enzyme substrate promiscuity can be potentially used for bioretrosynthetic approaches, leading to the design of alternative and more convenient routes to produce relevant molecules. In this perspective, plant-derived polyketides are extremely adaptable to those synthetic biological applications. Here, we present a combination of an in vitro CoA ligase activity assay coupled with a bacterial multigene expression system that leads to precursor-directed biosynthesis of 21 flavonoid derivatives. When the vast knowledge from protein databases is exploited, the herein presented procedure can be easily repeated with additional plant-derived polyketides. Lastly, we report an efficient in vivo expression system that can be further exploited to heterologously express pathways not necessarily related to plant polyketide synthases.

中文翻译：

使用组合和前体导向的生物合成方法合理设计类黄酮生产路线。

组合生物合成在设计合成电路和扩大新活性化合物的生产方面具有巨大潜力。多酶级联反应的研究对于提高我们对酶催化的知识非常有用。尤其是，酶底物混杂的阐明可潜在地用于生物维甲酸合成方法，从而导致设计产生相关分子的替代性和更方便的途径。从这个角度来看，植物来源的聚酮化合物非常适合那些合成生物学应用。在这里，我们提出一种体外组合CoA连接酶活性测定与细菌多基因表达系统结合，可导致21种类黄酮衍生物的前体定向生物合成。当利用蛋白质数据库中的大量知识时，可以使用其他植物衍生的聚酮化合物轻松地重复此处介绍的步骤。最后，我们报告了一种有效的体内表达系统，可以进一步利用该系统来异源表达与植物聚酮化合物合酶不一定相关的途径。

更新日期：2020-07-17

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