Streptomyces as Microbial Chassis for Heterologous Protein Expression

Soonkyu Hwang; Yongjae Lee; Ji Hun Kim; Gahyeon Kim; Hyeseong Kim; Woori Kim; Suhyung Cho; Bernhard O Palsson; Byung-Kwan Cho

doi:10.3389/fbioe.2021.804295

Streptomyces as Microbial Chassis for Heterologous Protein Expression

Front Bioeng Biotechnol. 2021 Dec 21:9:804295. doi: 10.3389/fbioe.2021.804295. eCollection 2021.

Authors

Soonkyu Hwang^{1

2}, Yongjae Lee^{1

2}, Ji Hun Kim^{1

2}, Gahyeon Kim^{1

2}, Hyeseong Kim^{1

2}, Woori Kim^{1

2}, Suhyung Cho^{1

2}, Bernhard O Palsson^{3

4

5}, Byung-Kwan Cho^{1

2

6}

Affiliations

¹ Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, South Korea.
² KAIST Institute for the BioCentury, Korea Advanced Institute of Science and Technology, Daejeon, South Korea.
³ Department of Bioengineering, University of California, San Diego, La Jolla, CA, United States.
⁴ Department of Pediatrics, University of California, San Diego, La Jolla, CA, United States.
⁵ Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Lyngby, Denmark.
⁶ Innovative Biomaterials Research Center, KAIST Institutes, Korea Advanced Institute of Science and Technology, Daejeon, South Korea.

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.

Keywords: chassis; heterologous expression; recombinant protein; secondary metabolite; streptomyces.

Publication types

Review