匹诺塞林合成生物学研究进展

Progress in synthetic biology of pinocembrin

摘要:

匹诺塞林是一种广泛存在于植物中的黄酮类化合物，具有很好的生物活性，如神经保护、抗菌、抗氧化等。2009年，匹诺塞林被CFDA批准为Ⅰ类注射新药，主要用于治疗急性脑卒中，现已经进入Ⅱ期临床试验阶段。匹诺塞林的良好成药性使其合成方法备受关注。匹诺塞林可以通过化学合成、植物提取和合成生物学技术制备。合成生物学技术是一种环境友好的工程化生物技术，代表未来匹诺塞林的合成发展方向。文中总结了利用合成生物学技术制备匹诺塞林的研究现状，并从选择酶的物种来源、提高丙二酰CoA含量、选择经济的底物及减弱中间产物的抑制作用等角度系统地总结了提高微生物合成匹诺塞林的策略。

Abstract:

Pinocembrin, belonging to flavanons, was isolated from various plants. Pinocembrin has a variety of pharmacological activities, such as neuroprotective effect, antimicrobial activity, and antioxidant efficacy. Pinocembrin was approved as classⅠdrugs to its phase Ⅱ clinical trial by CFDA in 2009, mainly used for the treatment of ischemic stroke. As a promising compound, the manufacturing technologies of pinocembrin, including chemical synthesis, extraction from plant and synthetic biology, have attracted many attentions. Compared with the first two technologies, synthetic biology has many advantages, such as environment-friendly and low-cost. Construction of biosynthetic pathway in microorganism offers promising results for large scale pinocembrin production by fermentation after taking lots of effective strategies. This article reviews some of recent strategies in microorganisms to improve the yield, with focus on the selection of appropriate the key enzyme sources, the supply of precursors and cofactors by microorganisms, the choice of substance and the level of the key enzyme expression.