System-level understanding of gene expression and regulation for engineering secondary metabolite production in Streptom

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APPLIED GENOMICS & SYSTEMS BIOTECHNOLOG - REVIEW

System‑level understanding of gene expression and regulation for engineering secondary metabolite production in Streptomyces Yongjae Lee1 · Namil Lee1 · Soonkyu Hwang1 · Kangsan Kim1 · Woori Kim1 · Jihun Kim1 · Suhyung Cho1 · Bernhard O. Palsson2,3,4 · Byung‑Kwan Cho1,5  Received: 1 June 2020 / Accepted: 27 July 2020 © Society for Industrial Microbiology and Biotechnology 2020

Abstract The gram-positive bacterium, Streptomyces, is noticed for its ability to produce a wide array of pharmaceutically active compounds through secondary metabolism. To discover novel bioactive secondary metabolites and increase the production, Streptomyces species have been extensively studied for the past decades. Among the cellular components, RNA molecules play important roles as the messengers for gene expression and diverse regulations taking place at the RNA level. Thus, the analysis of RNA-level regulation is critical to understanding the regulation of Streptomyces’ metabolism and secondary metabolite production. A dramatic advance in Streptomyces research was made recently, by exploiting high-throughput technology to systematically understand RNA levels. In this review, we describe the current status of the system-wide investigation of Streptomyces in terms of RNA, toward expansion of its genetic potential for secondary metabolite synthesis. Keywords  Streptomyces · Secondary metabolite · RNA · Transcription · Translation

Introduction As a dominant soil bacterium, Streptomyces plays an important role in carbon recycling by decomposing the debris of other organisms, including lignocellulose [26, 99]. In addition to the ability to decompose saprophytic compounds, Streptomyces species are noticed in aspects of their (1) morphogenetic characteristics, (2) industrial potential for heterologous protein production and (3) ability to produce pharmaceutically active compounds. First, streptomycetes undergo multiple developmental stages during the life cycle * Byung‑Kwan Cho [email protected] 1



Department of Biological Sciences and KI for the BioCentury, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea

2



Department of Bioengineering, University of California San Diego, La Jolla, CA 92093, USA

3

Department of Pediatrics, University of California San Diego, La Jolla, CA 92093, USA

4

Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2800 Lyngby, Denmark

5

Intelligent Synthetic Biology Center, Daejeon 34141, Republic of Korea



like fungi, and thus are attractive models to study bacterial development processes [34]. Second, Streptomyces is considered as an important industrial microorganism as the heterologous protein production host [72]. As a member of gram-positive bacteria lacking outer membrane, the proteins secreted by Streptomyces are directly released to the culture medium, simplifying protein purification steps. In addition, their protein secretion systems are well-characterized [3, 38]. Finally,