姜黄素类化合物生物合成研究进展

Research progresses in the biosynthesis of curcuminoids

摘要:

姜黄素类化合物是植物中一类稀少的二酮类化合物，存在于姜科、天南星科植物的块根或根茎中，是姜黄等植物中主要活性成分，因具有抗氧化、抗癌等诸多药理活性而被广泛应用于食品领域和新药研发中。因其苯环侧链取代基不同，姜黄素类化合物可进一步分为姜黄素、去甲氧基姜黄素、双去甲氧基姜黄素等。目前，姜黄素类化合物主要是通过植物提取法获得，产量远远不能满足市场需求。随着合成生物学和代谢工程技术的发展，采用生物合成法生产姜黄素类化合物开始受到研究人员的广泛关注。近年来，研究人员通过基因挖掘及酶学手段鉴定了姜黄中姜黄素合成途径中的关键酶，并在大肠杆菌Escherichia coli、耶氏解酯酵母Yarrowia lipolytica、恶臭假单胞菌Pseudomonas putida和米曲霉Aspergillus oryzae中重塑其生物合成途径，成功实现了其异源生物合成。文中首先介绍了姜黄素的生物活性及其应用、总结了姜黄中的姜黄素合成途径，并且讨论了姜黄素合成酶的催化机制，进而详尽综述了其生物合成的最新研究进展，特别是代谢工程策略方面，并对其未来发展方向进行了展望。

Abstract:

Curcuminoids are rare diketone compounds in plants and can be found in the rhizome of Curcuma longa as well as other Zingiberaceae and Araceae. Curcuminoids have been widely used in food and medical area owing to the yellow colors, as well as the antioxidant and many other pharmacological activities. Curcuminoids are a mixture of compounds containing curcumin, demethoxycurcumin and bisdemethoxycurcumin, which have distinct benzene ring substituents. Currently, curcuminoids are exclusively produced through plant extraction, which do not satisfy the meeting of the market demand. Empowered with new synthetic biology tools and metabolic engineering strategies, there is renewed interest in production of curcuminoids using microorganisms. Heterologous production of curcuminoids has been achieved using Escherichia coli, Yarrowia lipolytica, Pseudomonas putida and Aspergillus oryzae via engineering of curcuminoids biosynthesis pathway. In this review, we first describe the biological activities and various applications of curcuminoids. Next, we summarize the biosynthetic pathway of curcuminoids in Curcuma longa and discuss the catalytic mechanisms of curcumin synthases. Then, we thoroughly explore recent advances in the use of distinct microorganisms for the production of curcuminoids with a special focus on metabolic engineering strategies. Finally, we prospect the microbial production of curcuminoids by highlighting some promising techniques and approaches.