Systems Metabolic Engineering of Corynebacterium glutamicum to Create a Producer of L-Valine

Abstract

This review is devoted to the main approaches of systems metabolic engineering used in the development of Corynebacterium glutamicum–based producers of L-valine, an essential proteinogenic amino acid that is widely used as a feed additive. This direction of engineering is based on the concepts of systems biology, considering the living organism as a holistic system with complex interaction between elements. This review considers the following approaches: laboratory evolution as a way to obtain new mutations that increase L-valine production; the use of biosensors to select clones with such mutations; “omic” data obtained for C. glutamicum strains capable of producing L-valine and related amino acids; modification of genes encoding global regulatory factors; and modeling of metabolic pathways relevant to amino acid production in C. glutamicum using full genomic data. Each of the approaches is evaluated in terms of its effectiveness in increasing the productivity of strains and improving their technological characteristics. In addition, information is presented on modern methods of genome editing of C. glutamicum, without which it is impossible to carry out a large number of targeted modifications necessary for the realization of systems metabolic engineering approaches.