Schewe Hendrik, Mirata Marco Antonio, Schrader Jens
DECHEMA Research Institute, Biochemical Engineering, Frankfurt, Germany.
Adv Biochem Eng Biotechnol. 2015;148:251-86. doi: 10.1007/10_2015_321.
Isoprenoids represent a natural product class essential to living organisms. Moreover, industrially relevant isoprenoid molecules cover a wide range of products such as pharmaceuticals, flavors and fragrances, or even biofuels. Their often complex structure makes chemical synthesis a difficult and expensive task and extraction from natural sources is typically low yielding. This has led to intense research for biotechnological production of isoprenoids by microbial de novo synthesis or biotransformation. Here, metabolic engineering, including synthetic biology approaches, is the key technology to develop efficient production strains in the first place. Bioprocess engineering, particularly in situ product removal (ISPR), is the second essential technology for the development of industrial-scale bioprocesses. A number of elaborate bioreactor and ISPR designs have been published to target the problems of isoprenoid synthesis and conversion, such as toxicity and product inhibition. However, despite the many exciting applications of isoprenoids, research on isoprenoid-specific bioprocesses has mostly been, and still is, limited to small-scale proof-of-concept approaches. This review presents and categorizes different ISPR solutions for biotechnological isoprenoid production and also addresses the main challenges en route towards industrial application.
类异戊二烯是生物体必需的一类天然产物。此外，具有工业相关性的类异戊二烯分子涵盖了广泛的产品，如药物、香料和香精，甚至生物燃料。它们通常复杂的结构使得化学合成成为一项困难且昂贵的任务，并且从天然来源提取的产量通常较低。这导致了对通过微生物从头合成或生物转化进行类异戊二烯生物技术生产的深入研究。在此，代谢工程，包括合成生物学方法，首先是开发高效生产菌株的关键技术。生物过程工程，特别是原位产物去除（ISPR），是工业规模生物过程开发的第二项关键技术。已经发表了许多精心设计的生物反应器和ISPR设计，以解决类异戊二烯合成和转化的问题，如毒性和产物抑制。然而，尽管类异戊二烯有许多令人兴奋的应用，但对类异戊二烯特定生物过程的研究大多已经并且仍然局限于小规模的概念验证方法。本综述介绍并分类了用于生物技术生产类异戊二烯的不同ISPR解决方案，并讨论了走向工业应用过程中的主要挑战。
