Monoterpenoid biosynthesis by engineered microbes

Monoterpenoids are C10 isoprenoids and constitute a large family of natural products. They have been used as ingredients in food, cosmetics, and therapeutic products. Many monoterpenoids such as linalool, geraniol, limonene, and pinene are volatile and can be found in plant essential oils. Conventionally, these bioactive compounds are obtained from plant extracts by using organic solvents or by distillation method, which are costly and laborious if high-purity product is desired. In recent years, microbial biosynthesis has emerged as alternative source of monoterpenoids with great promise for meeting the increasing global demand for these compounds. However, current methods of production are not yet at levels required for commercialization. Production efficiency of monoterpenoids in microbial hosts is often restricted by high volatility of the monoterpenoids, a lack of enzymatic activity and selectivity, and/or product cytotoxicity to the microbial hosts. In this review, we summarize advances in microbial production of monoterpenoids over the past 3 years with particular focus on the key metabolic engineering strategies for different monoterpenoid products. We also provide our perspective on the promise of future endeavors to improve monoterpenoid productivity.