柠檬烯和红没药烯的微生物代谢工程

Advances in metabolic engineering for the microbial production of naturally occurring terpenes-limonene and bisabolene: a mini review

摘要:

柠檬烯和红没药烯均为植物天然产物，分别属于单萜类和倍半萜类化合物，能够预防和治疗癌症等多种疾病。以其作为前体物，还可以转化合成多种具有高附加值的工业产品，例如药品、保健品、化妆品及生物燃料等。目前柠檬烯和红没药烯的工业生产主要是通过植物提取法实现的，但从植物组织中提取柠檬烯和红没药烯存在着产物含量低和分离纯化困难等缺点。微生物代谢工程的快速发展为这些植物天然产物的生产提供了一条更具潜力的生物合成路线。利用微生物代谢工程技术构建生产这些有价值的植物天然产物的微生物细胞工厂具有绿色清洁、可持续发展和经济效益好等独特优势。文中系统综述了近年来代谢工程技术在微生物合成柠檬烯和红没药烯过程中的应用进展，包括所涉及的宿主菌株、关键酶、代谢途径及其改造等，并探讨了其未来发展方向。

Abstract:

Limonene (C10H16) and bisabolene (C15H24) are both naturally occurring terpenes in plants. Depending on the number of C5 units, limonene and bisabolene are recognized as representative monoterpenes and sesquiterpenes, respectively. Limonene and bisabolene are important pharmaceutical and nutraceutical products used in the prevention and treatment of cancer and many other diseases. In addition, they can be used as starting materials to produce a range of commercially valuable products, such as pharmaceuticals, nutraceuticals, cosmetics, and biofuels. The low abundance or yield of limonene and bisabolene in plants renders their isolation from plant sources non-economically viable. Isolation of limonene and bisabolene from plants also suffers from low efficiency and often requires harsh reaction conditions, prolonged reaction times, and expensive equipment cost. Recently, the rapid developments in metabolic engineering of microbes provide a promising alternative route for producing these plant natural products. Therefore, producing limonene and bisabolene by engineering microbial cells into microbial factories is becoming an attractive alternative approach that can overcome the bottlenecks, making it more sustainable, environmentally friendly and economically competitive. Here, we reviewed the status of metabolic engineering of microbes that produce limonene and bisabolene including microbial hosts, key enzymes, metabolic pathways and engineering of limonene/bisabolene biosynthesis. Furthermore, key challenges and future perspectives were discussed.