Microbial cell factories for the sustainable manufacturing of B vitamins

Acevedo‐Rocha, Carlos G.; Gronenberg, Luisa S.; Mack, Matthias; Commichau, Fabian M.; Genee, Hans Jasper

doi:10.1016/j.copbio.2018.07.006

Cited by 110 publications

(91 citation statements)

References 71 publications

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“…The industrial application of B. subtilis has developed rapidly in the last decades, and it has become the major microbial cell factory for many industrial products [ 44 , 45 ], including enzymes [ 46 ], heterologous proteins [ 31 ], antibiotics [ 47 ], vitamins [ 48 ], and amino acids [ 26 ]. Chemicals produced by B. subtilis also play an important role in various fields, such as food, feed, cosmetics, chemicals, and pharmaceuticals.…”

Section: Industrial Application Of Chemicals Produced By mentioning

confidence: 99%

“…In a recent review, microbial cell factories for the production of B vitamins were described in detail [ 48 ]. B. subtilis can be used to produce vitamins B 1 , B 2 , B 5 , B 6 , and B 7 , and many production strains were constructed by metabolic engineering or screened and selected from mutant libraries [ 48 ]. Vitamin B 2 is one of the most successful microbial fermentation products on an industrial scale [ 49 ].…”

Section: Vitamins As High-value Productsmentioning

confidence: 99%

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

Chuan²,

Fang³

et al. 2020

Microb Cell Fact

229

142

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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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Section: Industrial Application Of Chemicals Produced By mentioning

confidence: 99%

Section: Vitamins As High-value Productsmentioning

confidence: 99%

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

Chuan²,

Fang³

et al. 2020

Microb Cell Fact

229

142

View full text Add to dashboard Cite

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“…Exposure to the riboflavin analog roseoflavin isolated from Streptomyces davawensis was found to lead B. subtilis to spontaneous mutations and constitutive riboflavin overproduction (Ludwig et al, 2018). Roseoflavin negatively affects FMN-specific rib operon regulators (FMN riboswitches) and flavoenzymes in bacteria, and is used together with multiple copies of rib operon genes to select their overproducing strains (Acevedo-Rocha et al, 2019).…”

Section: Riboflavin Biosynthesis Regulationmentioning

confidence: 99%

“…However, the industrial process of riboflavin biosynthesis in B. subtilis is still dependent on several barely resolved issues, including RibR-regulation of FMN riboswitches limiting its production; unknown riboflavin pathway phosphatases; flavin reactivity damaging cells; and the absence of a transport system to export actively flavins in contrast to that of A. gossypii (Acevedo-Rocha et al, 2019). Wild-type B. subtilis cells rapidly convert intracellular riboflavin to FMN and FAD catalyzed by the bifunctional flavokinase/FAD synthetase RibC and cannot actively export flavins like A. gossypii.…”

Section: Riboflavin-producing Strain Improvementmentioning

confidence: 99%

Production of Vitamin B2 (Riboflavin) by Microorganisms: An Overview

Averianova

Balabanova

Son

et al. 2020

Front. Bioeng. Biotechnol.

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Riboflavin is a crucial micronutrient that is a precursor to coenzymes flavin mononucleotide and flavin adenine dinucleotide, and it is required for biochemical reactions in all living cells. For decades, one of the most important applications of riboflavin has been its global use as an animal and human nutritional supplement. Being well-informed of the latest research on riboflavin production via the fermentation process is necessary for the development of new and improved microbial strains using biotechnology and metabolic engineering techniques to increase vitamin B2 yield. In this review, we describe well-known industrial microbial producers, namely, Ashbya gossypii , Bacillus subtilis , and Candida spp. and summarize their biosynthetic pathway optimizations through genetic and metabolic engineering, combined with random chemical mutagenesis and rational medium components to increase riboflavin production.

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“…The rate‐limiting step in whole‐cell catalysis and biosynthesis process is the uptake of substrates, as transporters for substrates are usually insufficient or have low transport ability. To address this problem, specific transporters from exogenous organisms and certain evolved transporters have been expressed in strains that produce biofuels and biochemicals such as hydrocortisone, [ 85 ] B vitamins, [ 86 ] and L‐phenylalanine. [ 87 ]…”

Section: Applications Of Transport System Redesign In Microbial Manufmentioning

confidence: 99%

Transporter Engineering for Microbial Manufacturing

Zhu

Zhou

Wang

et al. 2020

Biotechnology Journal

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Microbes play an important role in biotransformation and biosynthesis of biofuels, natural products, and polymers. Therefore, microbial manufacturing has been widely used in medicine, industry, and agriculture. However, common strategies including enzyme engineering, pathway optimization, and host engineering are generally inadequate to obtain an efficient microbial production system. Transporter engineering provides an alternative strategy to promote the transmembrane transfer of substrates, intermediates, and final products in microbial cells and thus enhances production by alleviating feedback inhibition and cytotoxicity caused by final products. According to the current studies in transport engineering, native transporters usually have low expression and poor transportation ability, resulting in inefficient transport processes and microbial production. In this review, current approaches for transporter mining, characterization, and verification are comprehensively summarized. Practical approaches to enhance the transport system in engineered cells, such as balancing transporter overexpression and cell growth, and evolution of native transporters are discussed. Furthermore, the applications of transporter engineering in microbial manufacturing, including enhancement of substrate utilization, concentration of metabolic flux to the target pathway, and acceleration of efflux and recovery of products, demonstrate its outstanding advantages and promising prospects.

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Microbial cell factories for the sustainable manufacturing of B vitamins

Cited by 110 publications

References 71 publications

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

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

Production of Vitamin B2 (Riboflavin) by Microorganisms: An Overview

Transporter Engineering for Microbial Manufacturing

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