Department of Biology and Biological Engineering, Chalmers University of Technology, Göteborg SE41296, Sweden.
ACS Synth Biol. 2023 Jan 20;12(1):144-152. doi: 10.1021/acssynbio.2c00425. Epub 2022 Dec 19.
The flavonoid pinocembrin and its derivatives have gained increasing interest for their benefits on human health. While pinocembrin and its derivatives can be produced in engineered , yields remain low. Here, we describe novel strategies for improved biosynthesis of pinocembrin from glucose based on overcoming existing limitations in First, we identified cinnamic acid as an inhibitor of pinocembrin synthesis. Second, by screening for more efficient enzymes and optimizing the expression of downstream genes, we reduced cinnamic acid accumulation. Third, we addressed other limiting factors by boosting the availability of the precursor malonyl-CoA, while eliminating the undesired byproduct 2',4',6'-trihydroxy dihydrochalcone. After optimizing cultivation conditions, 80 mg/L pinocembrin was obtained in a shake flask, the highest yield reported for . Finally, we demonstrated that pinocembrin-producing strains could be further engineered to generate 25 mg/L chrysin, another interesting flavone. The strains generated in this study will facilitate the production of flavonoids through the pinocembrin biosynthetic pathway.
黄酮醇 pinocembrin 及其衍生物因其对人类健康的益处而受到越来越多的关注。虽然 pinocembrin 及其衍生物可以通过工程菌生产，但其产量仍然很低。在这里，我们描述了基于克服现有局限性来提高基于葡萄糖的 pinocembrin 生物合成的新策略。首先，我们发现肉桂酸是 pinocembrin 合成的抑制剂。其次，通过筛选更有效的酶并优化下游基因的表达，我们减少了肉桂酸的积累。第三，我们通过增加前体丙二酰辅酶 A 的可用性来解决其他限制因素，同时消除了不需要的副产物 2'，4'，6'-三羟基二氢查耳酮。在优化培养条件后，在摇瓶中获得了 80mg/L 的 pinocembrin，这是报道的最高产量。最后，我们证明了产 pinocembrin 的菌株可以进一步工程化，以产生另一种有趣的类黄酮 25mg/L 的白杨素。本研究中产生的菌株将通过 pinocembrin 生物合成途径促进类黄酮的生产。
