Bacillus subtilis : a universal cell factory for industry, agriculture, biomaterials and medicine

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Abstract

Due to its clear inherited backgrounds as well as simple and diverse genetic manipulation systems, Bacillus subtilis is the key Gram-positive model bacterium for studies on physiology and metabolism. Furthermore, due to its highly efficient protein secretion system and adaptable metabolism, it has been widely used as a cell factory for microbial production of chemicals, enzymes, and antimicrobial materials for industry, agriculture, and medicine. In this mini-review, we first summarize the basic genetic manipulation tools and expression systems for this bacterium, including traditional methods and novel engineering systems. Secondly, we briefly introduce its applications in the production of chemicals and enzymes, and summarize its advantages, mainly focusing on some noteworthy products and recent progress in the engineering of B. subtilis. Finally, this review also covers applications such as microbial additives and antimicrobials, as well as biofilm systems and spore formation. We hope to provide an overview for novice researchers in this area, offering them a better understanding of B. subtilis and its applications.

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Most cited references 102

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Bacillus subtilis antibiotics: structures, syntheses and specific functions.

Torsten Stein (2005)

The endospore-forming rhizobacterium Bacillus subtilis- the model system for Gram-positive organisms, is able to produce more than two dozen antibiotics with an amazing variety of structures. The produced anti-microbial active compounds include predominantly peptides that are either ribosomally synthesized and post-translationally modified (lantibiotics and lantibiotic-like peptides) or non-ribosomally generated, as well as a couple of non-peptidic compounds such as polyketides, an aminosugar, and a phospholipid. Here I summarize the structures of all known B. subtilis antibiotics, their biochemistry and genetic analysis of their biosyntheses. An updated summary of well-studied antibiotic regulation pathways is given. Furthermore, current findings are resumed that show roles for distinct B. subtilis antibiotics beyond the "pure" anti-microbial action: Non-ribosomally produced lipopeptides are involved in biofilm and swarming development, lantibiotics function as pheromones in quorum-sensing, and a "killing factor" effectuates programmed cell death in sister cells. A discussion of how these antibiotics may contribute to the survival of B. subtilis in its natural environment is given.

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Unravelling the structural and mechanistic basis of CRISPR-Cas systems.

John van der Oost, Edze R. Westra, Ryan N. Jackson … (2014)

Bacteria and archaea have evolved sophisticated adaptive immune systems, known as CRISPR-Cas (clustered regularly interspaced short palindromic repeats-CRISPR-associated proteins) systems, which target and inactivate invading viruses and plasmids. Immunity is acquired by integrating short fragments of foreign DNA into CRISPR loci, and following transcription and processing of these loci, the CRISPR RNAs (crRNAs) guide the Cas proteins to complementary invading nucleic acid, which results in target interference. In this Review, we summarize the recent structural and biochemical insights that have been gained for the three major types of CRISPR-Cas systems, which together provide a detailed molecular understanding of the unique and conserved mechanisms of RNA-guided adaptive immunity in bacteria and archaea.

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Developments in the use of Bacillus species for industrial production.

Marcus Schallmey, Ajay Singh, Owen P Ward (2004)

Bacillus species continue to be dominant bacterial workhorses in microbial fermentations. Bacillus subtilis (natto) is the key microbial participant in the ongoing production of the soya-based traditional natto fermentation, and some Bacillus species are on the Food and Drug Administration's GRAS (generally regarded as safe) list. The capacity of selected Bacillus strains to produce and secrete large quantities (20-25 g/L) of extracellular enzymes has placed them among the most important industrial enzyme producers. The ability of different species to ferment in the acid, neutral, and alkaline pH ranges, combined with the presence of thermophiles in the genus, has lead to the development of a variety of new commercial enzyme products with the desired temperature, pH activity, and stability properties to address a variety of specific applications. Classical mutation and (or) selection techniques, together with advanced cloning and protein engineering strategies, have been exploited to develop these products. Efforts to produce and secrete high yields of foreign recombinant proteins in Bacillus hosts initially appeared to be hampered by the degradation of the products by the host proteases. Recent studies have revealed that the slow folding of heterologous proteins at the membrane-cell wall interface of Gram-positive bacteria renders them vulnerable to attack by wall-associated proteases. In addition, the presence of thiol-disulphide oxidoreductases in B. subtilis may be beneficial in the secretion of disulphide-bond-containing proteins. Such developments from our understanding of the complex protein translocation machinery of Gram-positive bacteria should allow the resolution of current secretion challenges and make Bacillus species preeminent hosts for heterologous protein production. Bacillus strains have also been developed and engineered as industrial producers of nucleotides, the vitamin riboflavin, the flavor agent ribose, and the supplement poly-gamma-glutamic acid. With the recent characterization of the genome of B. subtilis 168 and of some related strains, Bacillus species are poised to become the preferred hosts for the production of many new and improved products as we move through the genomic and proteomic era.

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Author and article information

Contributors

Dawei Zhang:

ORCID: http://orcid.org/0000-0001-5555-6151

zhang_dw@tib.cas.cn

Journal

Journal ID (nlm-ta): Microb Cell Fact

Journal ID (iso-abbrev): Microb Cell Fact

Title: Microbial Cell Factories

Publisher: BioMed Central (London )

ISSN (Electronic): 1475-2859

Publication date (Electronic): 3 September 2020

Publication date PMC-release: 3 September 2020

Publication date Collection: 2020

Volume: 19

Electronic Location Identifier: 173

Affiliations

[1 ]GRID grid.413109.e, ISNI 0000 0000 9735 6249, College of Biotechnology, , Tianjin University of Science and Technology, ; Tianjin, 300457 China

[2 ]GRID grid.9227.e, ISNI 0000000119573309, Tianjin Institute of Industrial Biotechnology, , Chinese Academy of Sciences, ; Tianjin, 300308 China

[3 ]GRID grid.9227.e, ISNI 0000000119573309, Key Laboratory of Systems Microbial Biotechnology, , Chinese Academy of Sciences, ; Tianjin, 300308 China

[4 ]GRID grid.410726.6, ISNI 0000 0004 1797 8419, University of Chinese Academy of Sciences, ; Beijing, 100049 China

Author information

Dawei Zhang http://orcid.org/0000-0001-5555-6151

Article

Publisher ID: 1436

DOI: 10.1186/s12934-020-01436-8

PMC ID: 7650271

PubMed ID: 32883293

SO-VID: 4a5c8e0e-ff17-486e-a826-d66db6128337

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Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 4 July 2020

Date accepted : 27 August 2020

Funding

Funded by: National Key R&D Program of China

Award ID: 2018YFA0901600

Funded by: the Tianjin Science Fund for Distinguished Young Scholars

Award ID: 17JCJQJC45300

Funded by: Science and Technology Service Network (STS) Initiative of the Chinese Academy of Sciences (CAS)

Award ID: KFJ-STS-ZDTP-065

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ScienceOpen disciplines: Biotechnology

Keywords: bacillus subtilis,genetic manipulation,protein expression,biochemicals,enzymes,antimicrobials,biofilms

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ScienceOpen disciplines: Biotechnology

Keywords: bacillus subtilis, genetic manipulation, protein expression, biochemicals, enzymes, antimicrobials, biofilms

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Bacillus subtilis: a universal cell factory for industry, agriculture, biomaterials and medicine

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Genome Engineering using CRISPR

Most cited references 102

Bacillus subtilis antibiotics: structures, syntheses and specific functions.

Unravelling the structural and mechanistic basis of CRISPR-Cas systems.

Developments in the use of Bacillus species for industrial production.

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Cited by 101

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