Abstract
Streptomyces is a significant source of natural products that are used as therapeutic antibiotics, anticancer and antitumor agents, pesticides, and dyes. Recently, with the advances in metabolite analysis, many new secondary metabolites have been characterized. Moreover, genome mining approaches demonstrate that many silent and cryptic biosynthetic gene clusters (BGCs) and many secondary metabolites are produced in very low amounts under laboratory conditions. One strain many compounds (OSMAC), overexpression/deletion of regulatory genes, ribosome engineering, and promoter replacement have been utilized to activate or enhance the production titer of target compounds. Hence, the heterologous expression of BGCs by transferring to a suitable production platform has been successfully employed for the detection, characterization, and yield quantity production of many secondary metabolites. In this review, we introduce the systematic approach for the heterologous production of secondary metabolites from Streptomyces in Streptomyces and other hosts, the genome analysis tools, the host selection, and the development of genetic control elements for heterologous expression and the production of secondary metabolites.
Highlights
Received: 21 December 2020Accepted: 12 February 2021Published: 19 February 2021Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.Streptomyces is a group of filamentous, Gram-positive bacteria with a high GC content in their genomes
Some natural products were produced by the heterologous expression of biosynthetic gene cluster (BGC) involving transfer ribonucleic acids (tRNAs) synthases genes; for instance, the valanimycin BGC consists of the gene vlmL encoding Ser-tRNASer that produces seryltRNA, which may take part in the biosynthetic pathway of valanimycin [132]
The heterologous expression of natural products depends on two crucial factors: host engineering and BGC construction
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. The heterologous expression is a powerful strategy for discovering uncharacterized BGCs or increasing the production of many secondary metabolites BGCs. For example, hybrubins were successfully explored via the heterologous expression of the hbn BGC from Streptomyces variabilis Snt in S. lividans. The selection of hosts and other elements for heterologous expression depends on the targeted products. We provide insight into the systematic approach for the heterologous production of secondary metabolites from Streptomyces in Streptomyces and other hosts, such as Escherichia coli, Pseudomonas putida, Saccharomyces cerevisiae, Bacillus subtilis, Corynebacterium glutamicum, and Rhodococcus erythropolis. The tools for genome analysis assist with precisely identifying and cloning BGCs. This review presents the process for selecting hosts and developing genetic control elements for heterologous expression
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