Toward improved terpenoids biosynthesis: strategies to enhance the capabilities of cell factories

• Published in: Bioresources and bioprocessing Vol. 9; no. 1; pp. 6 - 33
• Main Authors: Fordjour, Eric, Mensah, Emmanuel Osei, Hao, Yunpeng, Yang, Yankun, Liu, Xiuxia, Li, Ye, Liu, Chun-Li, Bai, Zhonghu
• Format: Journal Article
• Language: English
• Published: Singapore Springer Singapore 24.01.2022; Springer Nature B.V; SpringerOpen
• Subjects: Biochemical Engineering; Biosynthesis; Cellular tolerance; Chemical industry; Chemical synthesis; Chemistry; Chemistry and Materials Science; Cytotoxicity; Dynamic regulation; Environmental Engineering/Biotechnology; Enzymatic activity; Enzymes; Factories; High-throughput screening; Industrial and Production Engineering; Industrial engineering; Intermediates; Manufacturing engineering; Metabolic engineering; Metabolites; Microorganisms; Natural products; Prenyltransferases; Promoter engineering; Protein engineering; RBS engineering; Regulatory sequences; Review; Selectivity; Terpenes; Terpenoids; Transcription; Protein engineering; Dynamic regulation; Terpenoids; RBS engineering; Modular engineering; Promoter engineering; Chromosomal integration; Cellular tolerance
• ISSN: 2197-4365; 2197-4365
• DOI: 10.1186/s40643-022-00493-8

Terpenoids form the most diversified class of natural products, which have gained application in the pharmaceutical, food, transportation, and fine and bulk chemical industries. Extraction from naturally occurring sources does not meet industrial demands, whereas chemical synthesis is often associated with poor enantio-selectivity, harsh working conditions, and environmental pollutions. Microbial cell factories come as a suitable replacement. However, designing efficient microbial platforms for isoprenoid synthesis is often a challenging task. This has to do with the cytotoxic effects of pathway intermediates and some end products, instability of expressed pathways, as well as high enzyme promiscuity. Also, the low enzymatic activity of some terpene synthases and prenyltransferases, and the lack of an efficient throughput system to screen improved high-performing strains are bottlenecks in strain development. Metabolic engineering and synthetic biology seek to overcome these issues through the provision of effective synthetic tools. This review sought to provide an in-depth description of novel strategies for improving cell factory performance. We focused on improving transcriptional and translational efficiencies through static and dynamic regulatory elements, enzyme engineering and high-throughput screening strategies, cellular function enhancement through chromosomal integration, metabolite tolerance, and modularization of pathways. Graphical Abstract