Bioprocess engineering for microbial synthesis and conversion of isoprenoids

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.