Development of Corynebacterium glutamicum as a platform strain for the enhanced production of non-ribosomal peptides and polyketides

Abstract

Non-ribosomal peptides (NRPs) and polyketides (PKs) are among the most important microbial metabolites used in a wide range of industries including pharmaceuticals, polymers, and natural dyes. Unfortunately, most of natural producers of NRPs and PKs are uncultivable or cannot be genetically manipulated, hindering the overproduction of target products. Correspondingly, the use of surrogate hosts with fast growth and genetically accessible has attracted increasing attention for NRPs and PKs production. On the other hand, Corynebacterium glutamicum has recently been receiving much attention as the next-generation microbial cell factory for the production of various high-value chemicals. However, there are only few studies have been conducted to explore the competence of C. glutamicum as a heterologous host for production of natural products, particularly NRPs and PKs. In this study, we reported the development of C. glutamicum as a platform bacterial strain for the enhanced production of indigoidine (NRP), 6-methylsalicylicacid (type 1 PK), premithramycinone and 8-demethoxy-steffimycin D (type II PK), and flaviolin (type III PK) by employing systems metabolic engineering strategies. Our works revealed the potential of C. glutamicum as a robust heterologous host and these could be a stepping stone towards the high-level bioproduction of NRPs and PKs.