Advances on systems metabolic engineering of Bacillus subtilis as a chassis cell

Xiang, Mengjie; Kang, Qian; Zhang, Dawei

doi:10.1016/j.synbio.2020.07.005

Cited by 33 publications

(16 citation statements)

References 107 publications

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“…Fajardo-Cavazos and Nicholson reported that freeze-dried B. subtilis spores in capsules can survive up to 3 years, not only in ambient conditions, but also in a round trip voyage to Mars with the presence of Galactic cosmic radiation and solar particle-event radiations [52]. In addition, B. subtilis is easy to modify genetically [78], which makes it easier to design recombinant spores targeting both the original SARS-CoV-2 and mutant viruses (Figure 1). Here, we successfully designed and engineered a type of recombinant B. subtilis, which can express sRBD on the surface of spores by encoding sRBD linked with the CotC gene.…”

Section: Discussionmentioning

confidence: 99%

RETRACTED: Expression of SARS-CoV-2 Spike Protein Receptor Binding Domain on Recombinant B. subtilis on Spore Surface: A Potential COVID-19 Oral Vaccine Candidate

Sung¹,

Liu²,

Wu³

et al. 2021

Vaccines

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Various types of vaccines, such as mRNA, adenovirus, and inactivated virus by injection, have been developed to prevent SARS-CoV-2 infection. Although some of them have already been approved under the COVID-19 pandemic, various drawbacks, including severe side effects and the requirement for sub-zero temperature storage, may hinder their applications. Bacillus subtilis (B. subtilis) is generally recognized as a safe and endotoxin-free Gram-positive bacterium that has been extensively employed as a host for the expression of recombinant proteins. Its dormant spores are extraordinarily resistant to the harsh environment in the gastrointestinal tract. This feature makes it an ideal carrier for oral administration in resisting this acidic environment and for release in the intestine. In this study, an engineered B. subtilis spore expressing the SARS-CoV-2 spike protein receptor binding domain (sRBD) on the spore surface was developed. In a pilot test, no adverse health event was observed in either mice or healthy human volunteers after three oral courses of B. subtilis spores. Significant increases in neutralizing antibody against sRBD, in both mice and human volunteers, after oral administration were also found. These findings may enable the further clinical developments of B. subtilis spores as an oral vaccine candidate against COVID-19 in the future.

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Section: Discussionmentioning

confidence: 99%

RETRACTED: Expression of SARS-CoV-2 Spike Protein Receptor Binding Domain on Recombinant B. subtilis on Spore Surface: A Potential COVID-19 Oral Vaccine Candidate

Sung¹,

Liu²,

Wu³

et al. 2021

Vaccines

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show abstract

“…B. subtilis has a short growth cycle, easy fermentation process, high genetic engineering operability, high genetic stability, clear metabolic networks, and no obvious codon preference. Most importantly, it has good protein secretion and expression capacity [42,43]. B. subtilis natto, mainly isolated from the fermented vegetable cheese natto, exhibited a multiple-effect fibrinolytic activity of approximately 40 IU/g (wet weight) [24].…”

Section: Production Strains Of Nkmentioning

confidence: 99%

Recent Advances in Nattokinase-Enriched Fermented Soybean Foods: A Review

Hou

et al. 2022

Foods

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With the dramatic increase in mortality of cardiovascular diseases (CVDs) caused by thrombus, this has sparked an interest in seeking more effective thrombolytic drugs or dietary nutriments. The dietary consumption of natto, a traditional Bacillus-fermented food (BFF), can reduce the risk of CVDs. Nattokinase (NK), a natural, safe, efficient and cost-effective thrombolytic enzyme, is the most bioactive ingredient in natto. NK has progressively been considered to have potentially beneficial cardiovascular effects. Microbial synthesis is a cost-effective method of producing NK. Bacillus spp. are the main production strains. While microbial synthesis of NK has been thoroughly explored, NK yield, activity and stability are the critical restrictions. Multiple optimization strategies are an attempt to tackle the current problems to meet commercial demands. We focus on the recent advances in NK, including fermented soybean foods, production strains, optimization strategies, extraction and purification, activity maintenance, biological functions, and safety assessment of NK. In addition, this review systematically discussed the challenges and prospects of NK in actual application. Due to the continuous exploration and rapid progress of NK, NK is expected to be a natural future alternative to CVDs.

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“… 20 Given the availability of an increasing number of cloning vectors and mutant host lines that are provided by the Bacillus Genetic Stock Center (BGSC), 21 many strains can be transformed using systematic metabolic engineering to obtain mutant strains that meet production requirements. 22 For example, B. subtilis WB600 and B. subtilis WB800 were constructed from B. subtilis 168 by knocking out six and eight protease genes, respectively. 20 , 23 Although some proteases may be of interest to the industry, their activity generally limits the overall efficiency of heterologous protein production.…”

Section: The B Subtilis Expression Platformmentioning

confidence: 99%

The multifunctionality of expression systems in Bacillus subtilis: Emerging devices for the production of recombinant proteins

Souza

Guimarães

Pereira

et al. 2021

Exp Biol Med (Maywood)

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Bacillus subtilis is a successful host for producing recombinant proteins. Its GRAS (generally recognized as safe) status and its remarkable innate ability to absorb and incorporate exogenous DNA into its genome make this organism an ideal platform for the heterologous expression of bioactive substances. The factors that corroborate its value can be attributed to the scientific knowledge obtained from decades of study regarding its biology that has fostered the development of several genetic engineering strategies, such as the use of different plasmids, engineering of constitutive or double promoters, chemical inducers, systems of self-inducing expression with or without a secretion system that uses a signal peptide, and so on. Tools that enrich the technological arsenal of this expression platform improve the efficiency and reduce the costs of production of proteins of biotechnological importance. Therefore, this review aims to highlight the major advances involving recombinant expression systems developed in B. subtilis, thus sustaining the generation of knowledge and its application in future research. It was verified that this bacterium is a model in constant demand and studies of the expression of recombinant proteins on a large scale are increasing in number. As such, it represents a powerful bacterial host for academic research and industrial purposes.

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Advances on systems metabolic engineering of Bacillus subtilis as a chassis cell

Cited by 33 publications

References 107 publications

RETRACTED: Expression of SARS-CoV-2 Spike Protein Receptor Binding Domain on Recombinant B. subtilis on Spore Surface: A Potential COVID-19 Oral Vaccine Candidate

RETRACTED: Expression of SARS-CoV-2 Spike Protein Receptor Binding Domain on Recombinant B. subtilis on Spore Surface: A Potential COVID-19 Oral Vaccine Candidate

Recent Advances in Nattokinase-Enriched Fermented Soybean Foods: A Review

The multifunctionality of expression systems in Bacillus subtilis: Emerging devices for the production of recombinant proteins

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