Tools for metabolic engineering in Streptomyces

Abstract

During the last few decades, Streptomycetes have shown to be a very important and adaptable group of bacteria for the production of various beneficial secondary metabolites. These secondary metabolites have been of great interest in academia and the pharmaceutical industries. To date, a vast variety of techniques and tools for metabolic engineering of relevant structural biosynthetic gene clusters have been developed. The main aim of this review is to summarize and discuss the published literature on tools for metabolic engineering of Streptomyces over the last decade. These strategies involve precursor engineering, structural and regulatory gene engineering, and the up or downregulation of genes, as well as genome shuffling and the use of genome scale metabolic models, which can reconstruct bacterial metabolic pathways to predict phenotypic changes and hence rationalize engineering strategies. These tools are continuously being developed to simplify the engineering strategies for this vital group of bacteria.

Keywords: Streptomycetes; genome scale metabolic models; industrial production; metabolic engineering; secondary metabolites.

Figure 1. StreptomeDB GUI output.

Figure 2. Metabolic engineering of various genes in the glycolytic pathway for improved clavulanic acid production. (1) Disruption of gap genes in order to remove competing pathways and hence improve clavulanic acid production. (2) Duplication of pah2 gene encoding a proclavaminate amidino hydrolase, one of the precursors in clavulanic acid production. (3) Increasing cas2 gene production by using recombinant plasmids, which codes for clavaminate synthase gene, another precursor in clavulanic acid production.