Engineering a ComA Quorum-Sensing circuit to dynamically control the production of Menaquinone-4 in Bacillus subtilis

Yuan, Panhong; Sun, Guoyun; Cui, Shumao; Wu, Yaokang; Liu, Yanfeng; Li, Jianghua; Du, Guocheng; Liu, Long

doi:10.1016/j.enzmictec.2021.109782

Cited by 8 publications

(12 citation statements)

References 39 publications

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“…Along with random mutagenesis, rational strain engineering strategies such as metabolic engineering have been conducted to increase the MK-7 biosynthesis in Bacillus [ 92 , 93 , 95 , 96 ]. Over the past few years, the MK-7 biosynthesis pathway and many enzymes involved in biosynthesis have been studied, which facilitates metabolic engineering [ 30 ].…”

Section: Production Of Vitamin K Using Engineered Microorganismsmentioning

confidence: 99%

“…The resulting BS20-QT strain produced 310 mg/L of MK-7 [ 97 ]. Another study reported the increased production of MK-4 in B. subtilis using the QS system [ 96 ]. The authors developed the PhrQ-RapQ-ComA QS system and introduced it into the recombinant B. subtilis , overexpressing the ispH , crtE , and menA for dynamic control of MK-4 biosynthesis by the QS system.…”

Section: Production Of Vitamin K Using Engineered Microorganismsmentioning

confidence: 99%

“…The authors developed the PhrQ-RapQ-ComA QS system and introduced it into the recombinant B. subtilis , overexpressing the ispH , crtE , and menA for dynamic control of MK-4 biosynthesis by the QS system. The resulting BC04 strain produced 217 mg/L of MK-4 in a 3L fermenter [ 96 ]. These results suggested that cell growth and efficient synthesis of the vitamin K in B. subtilis can be dynamically balanced by the QS system, resulting in increased vitamin K production.…”

Section: Production Of Vitamin K Using Engineered Microorganismsmentioning

confidence: 99%

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Production of Vitamin K by Wild-Type and Engineered Microorganisms

et al. 2022

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Vitamin K is a fat-soluble vitamin that mainly exists as phylloquinone or menaquinone in nature. Vitamin K plays an important role in blood clotting and bone health in humans. For use as a nutraceutical, vitamin K is produced by natural extraction, chemical synthesis, and microbial fermentation. Natural extraction and chemical synthesis methods for vitamin K production have limitations, such as low yield of products and environmental concerns. Microbial fermentation is a more sustainable process for industrial production of natural vitamin K than two other methods. Recent advanced genetic technology facilitates industrial production of vitamin K by increasing the yield and productivity of microbial host strains. This review covers (i) general information about vitamin K and microbial host, (ii) current titers of vitamin K produced by wild-type microorganisms, and (iii) vitamin K production by engineered microorganisms, including the details of strain engineering strategies. Finally, current limitations and future directions for microbial production of vitamin K are also discussed.

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Section: Production Of Vitamin K Using Engineered Microorganismsmentioning

confidence: 99%

Section: Production Of Vitamin K Using Engineered Microorganismsmentioning

confidence: 99%

Section: Production Of Vitamin K Using Engineered Microorganismsmentioning

confidence: 99%

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Production of Vitamin K by Wild-Type and Engineered Microorganisms

et al. 2022

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“…23 In addition to transcription strength, attempts have been made to postpone the initiation of QS promoters by reducing their affinity for their activators by deleting the activator binding site ComA-box of the QS promoter in ComQXPA. 24 However, such modifications restricted to QS promoters render induction initiation closely associated with induction strength. Enhanced induction strength generally comes with a premature induction initiation, 20,23 whereas induction can be delayed at the expense of significantly reduced induction strength.…”

Section: ■ Introductionmentioning

confidence: 99%

“…Enhanced induction strength generally comes with a premature induction initiation, 20,23 whereas induction can be delayed at the expense of significantly reduced induction strength. 24 Although P srfA -mediated gene expression can be postponed without sacrificing intensity by adding adequate glucose, excessive glucose seriously interferes with other metabolic pathways and adds to costs. 25 Many components are involved in QS regulation, and genetic modifications beyond QS promoters might provide an opportunity to disrupt the status quo.…”

Section: ■ Introductionmentioning

confidence: 99%

Efficient, Flexible Autoinduction Expression Systems with Broad Initiation in Bacillus subtilis

Tong

et al. 2021

ACS Synth. Biol.

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Low expression levels and inflexible induction initiation have been the main obstacles to produce proteins using bacterial quorum sensing (QS). The typical QS system in Bacillus subtilis, ComQXPA, activates the promoter PsrfA using ComX and ComA as an auto-inducer and a promoter activator, respectively. Here, we developed a series of flexible autoinduction expression systems in B. subtilis WB600 based on ComQXPA using a super-folder green fluorescent protein as the reporter. The −35 region of PsrfA was replaced with corresponding conserved sequences of σA-dependent promoters, yielding P1 with 85% enhanced strength. We then applied a semi-rational design within the spacer between the −35 and −15 regions of P1 to generate the QS promoter PS1E, which generated 8.22-fold more expression than PsrfA. Based on PS1E, we finally obtained three types of autoinduction expression systems with initiation ranging from 1.5–9.5 h by optimizing the combination of the promoters for ComX and ComA. The yield of Bacillus deramificans pullulanase generated using autoinduction expression systems in B. subtilis reached 80.2 U/mL, which was 36% more than that of the most powerful constitutive promoter P566. Flexible autoinduction expression systems with diverse dynamic features have considerable potential for improving protein expression and metabolite production in B. subtilis.

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