Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Buffalo, NY 14260, USA.
Appl Environ Microbiol. 2011 May;77(10):3451-60. doi: 10.1128/AEM.02186-10. Epub 2011 Mar 25.
Plant polyphenols have been the subject of several recent scientific investigations since many of the molecules in this class have been found to be highly active in the human body, with a plethora of health-promoting activities against a variety of diseases, including heart disease, diabetes, and cancer, and with even the potential to slow aging. Further development of these potent natural therapeutics hinges on the formation of robust industrial production platforms designed using specifically selected as well as engineered protein sources along with the construction of optimal expression platforms. In this work, we first report the investigation of various stilbene synthases from an array of plant species considering structure-activity relationships, their expression efficiency in microorganisms, and their ability to synthesize resveratrol. Second, we looked into the construct environment of recombinantly expressed stilbene synthases, including different promoters, construct designs, and host strains, to create an Escherichia coli strain capable of producing superior resveratrol titers sufficient for commercial usage. Further improvement of metabolic capabilities of the recombinant strain aimed at improving the intracellular malonyl-coenzyme A pool, a resveratrol precursor, resulted in a final improved titer of 2.3 g/liter resveratrol.
植物多酚类化合物是近年来科学研究的热点，因为该类化合物中的许多分子在人体内具有高度的活性，对多种疾病（包括心脏病、糖尿病和癌症）具有多种促进健康的作用，甚至有延缓衰老的潜力。这些有效天然疗法的进一步发展取决于使用经过特别选择和工程化的蛋白质来源构建强大的工业生产平台，以及构建最佳表达平台。在这项工作中，我们首先报告了对来自多种植物物种的各种芪合酶的研究，考虑了结构-活性关系、它们在微生物中的表达效率以及它们合成白藜芦醇的能力。其次，我们研究了重组表达芪合酶的构建环境，包括不同的启动子、构建设计和宿主菌株，以创建一种能够产生足够高商业用途白藜芦醇滴度的大肠杆菌菌株。旨在提高白藜芦醇前体细胞内丙二酰辅酶 A 池的代谢能力的重组菌株的进一步改进，最终使白藜芦醇的产量提高到 2.3 g/L。
