Transcriptome analysis of Corynebacterium glutamicum in the process of recombinant protein expression in bioreactors

Abstract

Corynebacterium glutamicum (C. glutamicum) is a favorable host cell for the production of recombinant proteins, such as important enzymes and pharmaceutical proteins, due to its excellent potential advantages. Herein, we sought to systematically explore the influence of recombinant protein expression on the transcription and metabolism of C. glutamicum. Two C. glutamicum strains, the wild-type strain and an engineered strain expressing enhanced green fluorescent protein (EGFP), were cultured in parallel in 5-L bioreactors to study the change in metabolism in the process of EGFP expression. The results revealed that EGFP expression had great effects on the growth and metabolism of C. glutamicum and contributed to metabolism-like anaerobic conditions as follows: glycolysis was enhanced, the TCA cycle was shunted, and Glu, Val, Met, lactate and acetate were accumulated to produce sufficient ATP for EGFP production and transfer. Many differentially expressed genes related to ribosomal protein, transcriptional regulators, and energy metabolism were found to be expressed in the presence of EGFP, laying the foundation for identifying genomic loci to change the flow of the host cell metabolism to improve the ability of expressing foreign proteins in C. glutamicum.

Recent advances in metabolic engineering of Corynebacterium glutamicum as a potential platform microorganism for biorefinery

“…C. glutamicum is a gram‐positive, non‐pathogenic strain currently used for the commercial production of l ‐lysine and l ‐glutamate . To produce amino acids in an economic manner, the genetic and physical properties of C. glutamicum have been extensively studied . Genetic engineering tools and strategies have been developed to enhance the uptake of natural substrates, such as glucose, fructose, maltose, mannose, ribose, and sucrose, and thereby to improve the yield of biochemical production .…”