Genome-Reduced Corynebacterium glutamicum Fit for Biotechnological Applications

Abstract

Genome minimization ultimately leads to the smallest genome sustaining life of a given cell, however, growth of this cell may be very slow and may require multiple supplements e.g. to overcome amino acid auxotrophies. By contrast, genome reduction of industrially relevant bacteria such as Corynebacterium glutamicum does not aim at generating minimal cells. Rather chassis cells are developed that are as fit as the wild type with respect to a target function: for example growth of C. glutamicum in glucose minimal medium. Thus, a balance between reducing the burden of expressed genes while maintaining fast growth with glucose without the requirement for supplements such as amino acids is required. Here, the application of this concept to C. glutamicum is discussed. Moreover, an outlook on how the advent of genome editing by CRISPR-Cas9 or CRISPR-Cpf1 impacts genome reduction and how highly parallel genome editing must be met by highly parallel strain characterization is presented. Finally, metabolic engineering approaches for the overproduction of amino acids, organic acids, terpenoids and diamines making use of genome-reduced C. glutamicum strains are detailed.

Metabolic Engineering of Corynebacterium glutamicum for Sustainable Production of the Aromatic Dicarboxylic Acid Dipicolinic Acid

“…Therefore, L-lysine overproducing C. glutamicum are ideal hosts for production of compounds that can be derived from L-lysine or intermediates of L-lysine biosynthesis. A strong metabolic engineering tool box is available for C. glutamicum including traditional mutagenesis and selection [39], rational strain design [40], genome reduction [41,42] and the CRISPR tools [43], including CRISPR interference [44]. Based on the strong performance of L-lysine producing C. glutamicum strains [38], production of L-lysine derived products has been enabled by extension of L-lysine biosynthesis.…”