Biotechnology and Bioprocess Engineering 2020; 25(6): 872-885  
Engineering Bacillus subtilis Cells as Factories: Enzyme Secretion and Value-added Chemical Production
Ken-ichi Yoshida and Jan Maarten van Dijl
Ken-ichi Yoshida*
Department of Science, Technology and Innovation, Kobe University, Kobe, Hyogo 657 8501, Japan
Tel/Fax: +81-78-803-5891
Jan Maarten van Dijl*
Department of Medical Microbiology, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, The Netherlands
Tel: +31-50-361-5187
Received: April 6, 2020; Revised: May 12, 2020; Accepted: May 18, 2020; Published online: December 31, 2020.
© The Korean Society for Biotechnology and Bioengineering. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Bacillus subtilis has been studied for more than half a century, ever since the dawn of molecular biology, as a representative Gram-positive bacterium and cell factory. Two characteristic capacities of B. subtilis, namely its natural competence for DNA uptake and high-level enzyme secretion, have been investigated and exploited intensively during these long years. As a consequence, this bacterium has evolved into an excellent platform for synthetic biological research and development. In this review, we outline basic concepts for B. subtilis cell factory engineering, and we describe several examples of its applications in the production of proteins and high-value metabolites. In particular, we highlight engineering approaches that can make the already very efficient Bacillus protein secretion pathways even more efficient for the production of enzymes and pharmaceutical proteins. We further showcase examples of metabolic engineering in B. subtilis based on synthetic biology principles to produce various high-value or healthpromoting substances, especially inositol stereoisomers. We conclude that the versatile traits of B. subtilis, combined with multi-omics approaches and rapidly developing technologies for genome engineering and high-throughput screening enable us to modify and optimize this bacterium’s metabolic circuits to deliver compounds that are needed for a green and sustainable society as well as a healthy population.
Keywords: Bacillus subtilis, enzyme, secretion, inositol, bioconversion

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