CRISPR-Cas system in microbial hosts for terpenoid production

Terpenoids represent the largest group of secondary metabolites with variable structures and functions. Terpenoids are well known for their beneficial application in human life, such as pharmaceutical products, vitamins, hormones, anticancer drugs, cosmetics, flavors and fragrances, foods, agriculture, and biofuels. Recently, engineering microbial cells have been provided with a sustainable approach to produce terpenoids with high yields. Noticeably, the clustered regularly interspaced short palindromic repeats (CRISPR)-associated (Cas) system has emerged as one of the most efficient genome-editing technologies to engineer microorganisms for improving terpenoid production. In this review, we summarize the application of the CRISPR-Cas system for the production of terpenoids in microbial hosts such as Escherichia coli, Saccharomyces cerevisiae, Corynebacterium glutamicum, and Pseudomonas putida. CRISPR-Cas9 deactivated Cas9 (dCas9)-based CRISPR (CRISPRi), and the dCas9-based activator (CRISPRa) have been used in either individual or combinatorial systems to control the metabolic flux for enhancing the production of terpenoids. Finally, the prospects of using the CRISPR-Cas system in terpenoid production are also discussed.