Combing with redox regulation via quorum-sensing system and fermentation strategies for improving D-pantothenic acid production

Qin, Hai-Bin; Zhou, Junping; Zhang, Bo; Liu, Zhiqiang; Zheng, Yu‐Guo

doi:10.1016/j.procbio.2022.08.012

Cited by 4 publications

(2 citation statements)

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“…32 Qin et al further achieved a DPA yield in E. coli up to 4.19 g/L in shake flasks by overexpression of the genes zwf and nadK, and dynamic regulation of redox. 33 In addition, systematic metabolic engineering in E. coli led to an increased DPA yield of 2.30 g/L. 34 Later, Li et al increased DPA yields to 5.78 g/L in an engineered strain by strengthening the precursor pool, regulating the gene gdhA, and decreasing acetate.…”

Section: Introductionmentioning

confidence: 99%

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Dynamically Regulating Glucose Uptake to Reduce Overflow Metabolism with a Quorum-Sensing Circuit for the Efficient Synthesis of d-Pantothenic Acid in Bacillus subtilis

Yuan,

Xu,

Mao

et al. 2023

ACS Synth. Biol.

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In response to a high concentration of glucose, Bacillus subtilis, a microbial chassis for producing many industrial metabolites, rapidly takes up glucose using the phosphotransferase system (PTS), leading to overflow metabolism, a common phenomenon observed in many bacteria. Although overflow metabolism affects cell growth and reduces the production of many metabolites, effective strategies that reduce overflow metabolism while maintaining normal cell growth remain to be developed. Here, we used a quorum sensing (QS)-mediated circuit to tune the glucose uptake rate and thereby relieve overflow metabolism in an engineered B. subtilis for producing d-pantothenic acid (DPA). A low-efficiency non-PTS system was used for glucose uptake at the early growth stages to avoid a rapid glycolytic flux, while an efficient PTS system, which was activated by a QS circuit, was automatically activated at the late growth stages after surpassing a threshold cell density. This strategy was successfully applied as a modular metabolic engineering process for the high production of DPA. By enhancing the translation levels of key enzymes (3-methyl-2-oxobutanoate hydroxymethytransferase, pantothenate synthetase, aspartate 1-decarboxylase proenzyme, 2-dehydropantoate 2-reductase, dihydroxy-acid dehydratase, and acetolactate synthase) with engineered 5′-untranslated regions (UTRs) of mRNAs, the metabolic flux was promoted in the direction of DPA production, elevating the yield of DPA to 5.11 g/L in shake flasks. Finally, the engineered B. subtilis produced 21.52 g/L of DPA in fed-batch fermentations. Our work not only revealed a new strategy for reducing overflow metabolism by adjusting the glucose uptake rate in combination with promoting the translation of key metabolic enzymes through engineering the 5′-UTR of mRNAs but also showed its power in promoting the bioproduction of DPA in B. subtilis, exhibiting promising application prospects.

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Section: Introductionmentioning

confidence: 99%

“…Qin et al further achieved a DPA yield in E. coli up to 4.19 g/L in shake flasks by overexpression of the genes zwf and nadK , and dynamic regulation of redox . In addition, systematic metabolic engineering in E.…”

Section: Introductionmentioning

confidence: 99%