Abstract
Heterologous production of recombinant proteins is gaining increasing interest in biotechnology with respect to productivity, scalability, and wide applicability. The members of genus Streptomyces have been proposed as remarkable hosts for heterologous production due to their versatile nature of expressing various secondary metabolite biosynthetic gene clusters and secretory enzymes. However, there are several issues that limit their use, including low yield, difficulty in genetic manipulation, and their complex cellular features. In this review, we summarize rational engineering approaches to optimizing the heterologous production of secondary metabolites and recombinant proteins in Streptomyces species in terms of genetic tool development and chassis construction. Further perspectives on the development of optimal Streptomyces chassis by the design-build-test-learn cycle in systems are suggested, which may increase the availability of secondary metabolites and recombinant proteins.
Highlights
Many efforts have been made to produce recombinant proteins on a large industrial scale
linear-to-circular homologous recombination (LCHR) occurs between the linear insert and the circular vector using the Red-α/β protein derived from the lambda red phage, whereas linear-to-linear HR (LLHR) occurs between two linearized DNA fragments using RecE/T from a Rac prophage (Fu et al, 2012)
Several Streptomyces species previously used for heterologous hosts due to their general and specific advantages would be the starting strains, and their genomes will be minimized by removing all of their native biosynthetic gene clusters (BGCs) and genes with negative effects on heterologous expression, such as insertion sequence (IS) elements, resulting in the “minimized Streptomyces chassis library.”
Summary
Many efforts have been made to produce recombinant proteins on a large industrial scale. There are some drawbacks compared to other heterologous hosts in terms of the robustness of growth, genetic tools, and genetic information To overcome these limitations, rational engineering approaches for heterologous protein production have been developed for Streptomyces, as presented (Figure 1). LCHR occurs between the linear insert and the circular vector using the Red-α/β protein derived from the lambda red phage, whereas LLHR occurs between two linearized DNA fragments using RecE/T from a Rac prophage (Fu et al, 2012) These methods are rapid and highly efficient for cloning small- or medium-sized BGCs, such as gougerotin (Jiang et al, 2013), streptoketides (Qian et al, 2020), and oxytetracycline (Yin et al, 2016).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
