Modular Metabolic Engineering for Biobased Chemical Production. Issue 2 (February 2019)

• Record Type: Journal Article
• Authors: Lu, Hongyuan; Villada, Juan C.; Lee, Patrick K.H.
• Is Part Of: Trends in biotechnology. Volume 37:Issue 2(2019)
• Page Start: 152
• Page End: 166
• Publication Date: 2019-02
• Subjects: modular engineering -- coculture -- biobased chemicals -- genome-scale metabolic model; Biotechnology -- Periodicals; Biochemical engineering -- Periodicals; Genetic engineering -- Periodicals; Industrial microbiology -- Periodicals; 660.605
• DOI: 10.1016/j.tibtech.2018.07.003
• Languages: English
• ISSNs: 0167-7799

Abstract

Abstract : Microorganisms can manufacture a wide range of biobased chemicals that are useful for diverse industrial applications. However, the overexpression of heterologous enzymes in recombinant strains often leads to metabolic imbalance, resulting in growth retardation and suboptimal production of the target compounds. Here we discuss the recent development of modular metabolic engineering approaches that enable the global fine-tuning of engineered pathways by modularizing the synthetic pathway in single or multiple hosts. In particular, we highlight applications with microbial consortia. To build a vibrant biobased economy, multivariate modular metabolic engineering (MMME), modular coculture engineering (MCE), and spatiotemporal and integrative genome-scale metabolic modeling can be exploited to expedite strain optimization and improve the production of a broad variety of high-value biobased chemicals. Highlights: Microbial cell factories for the production of biobased chemicals are a promising route to achieve a sustainable future. However, it is essential to address metabolic imbalances caused by engineered pathways in microbial hosts. Multivariate modular metabolic engineering (MMME) and modular coculture engineering (MCE) can reconstitute the metabolic balance by modularizing the synthetic pathways and globally fine-tuning the expression levels of pathway modules in single or multiple hosts. The cross-cultural modular design of MCE significantly reduces the time and difficulty of reconstituting long synthetic pathways in a single host and polycultures enable the synthesis of complex compounds. Computer-aided genome minimization coupled with designing orthogonal metabolic pathways (independent from biomass synthesis) can open new paths to optimize microbial strains in a modular synthetic community.