Recent Advances in Synthetic Biology for the Engineering of Lactic Acid Bacteria
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pISSN 1226-8372 eISSN 1976-3816
REVIEW PAPER
Recent Advances in Synthetic Biology for the Engineering of Lactic Acid Bacteria Jaewoo Son and Ki Jun Jeong
Received: 2 February 2020 / Revised: 29 February 2020 / Accepted: 3 March 2020
© The Korean Society for Biotechnology and Bioengineering and Springer 2020
Abstract Lactic acid bacteria (LAB) have a long historical record of usage in many types of food-related bioprocesses, and as LAB have been found to have intrinsic beneficial effects on human health, interest in using LAB as a medical treatment has increased. Moreover, recent advances in synthetic biology have enabled the engineering of so-called “smart” bacteria with the native characteristics of LAB. With various synthetic parts for gene expression, genome editing, and genetic circuits, gene expression can be precisely regulated in LAB. Moreover, LAB have been successfully developed as potential hosts for therapeutics to detect and control specific diseases or to deliver drug molecules. In this review, we outline the recent development of synthetic parts and approaches for the engineering of LAB. We also discuss the potential application of synthetic biology for the utilization of LAB as living therapeutics. Keywords: lactic acid bacteria, synthetic biology, synthetic parts, genome editing, living therapeutics
1. Introduction Lactic acid bacteria (LAB) are a well-known group of nonsporulating Gram-positive bacteria. This group of bacteria is composed of species from several different genera, including Lactococcus, Lactobacillus, Leuconostoc, Jaewoo Son, Ki Jun Jeong Department of Chemical and Biomolecular Engineering, BK21 Plus program, KAIST, Daejeon 34141, Korea Ki Jun Jeong* Institute for The BioCentury, KAIST, Daejeon 34141, Korea Tel: +82-42-350-3934; Fax: +82-42-350-3910 E-mail: [email protected]
Pediococcus, Streptococcus, and Oenococcus [1]. LAB have been used in manufacturing of fermented foods such as kimchi, yogurt, and vegetables owing to their fermentation properties for promoting natural preservation and taste development [2]. In this regard, LAB have a long historical record of usage in many types of food-related biotechnology processes and recently, LAB are gaining attention for novel uses, owing to their safety for human and animal consumption, metabolic versatility, and wide ecological niche [3]. As microbial cell factories, LAB have several beneficial properties. Firstly, compared to other microorganisms, simple carbon metabolism, effective energy consumption, and a small genome (~2-3 Mb) make LAB crucial candidates for metabolic engineering strategies that are focused on regulating synthetic pathways to produce important fermentation end-products, e.g., sweeteners, flavors, aroma compounds, exopolysaccharides, and even vitamins [4-8]. Secondly, LAB, bifidobacteria, Escherichia coli Nissle 1917, and yeasts (Saccharomyces cerevisiae, Saccharomyces boulardii, Kluyveromyces lactis, Pichia pastoris, etc.) are recognized as prospective probiotics, which are defined as “live microorganism
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