Fatty Acid Production by Enhanced Malonyl-CoA Supply in Escherichia coli

Kaku, Moena; Ishidaira, Mei; Satoh, Shusaku; Ozaki, Miho; Kohari, Daisuke; Chohnan, Shigeru

doi:10.1007/s00284-022-02969-4

Cited by 4 publications

(2 citation statements)

References 51 publications

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“…Overexpression of matB , matC , accABCD , fumC , knockout of sucC , and other strategies in E. coli can increase the intracellular malonyl-CoA concentration. ,− This strategy has been used in the microbial biosynthesis of curcumin but with limited results. ,,, The synthesis of fatty acids consumes malonyl-CoA but is highly correlated to the growth of the strain. Therefore, the fatty acid elongation cycle needs to be inhibited but cannot be blocked.…”

Section: Discussionmentioning

confidence: 99%

Efficient De Novo Biosynthesis of Curcumin in Escherichia coli by Optimizing Pathway Modules and Increasing the Malonyl-CoA Supply

Chen,

Wang,

Wang

et al. 2023

J. Agric. Food Chem.

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Curcumin is a natural phenylpropanoid compound with various biological activities and is widely used in food and pharmaceuticals. A de novo curcumin biosynthetic pathway was constructed in Escherichia coli BL21(DE3). Optimization of the curcumin biosynthesis module achieved a curcumin titer of 26.8 ± 0.6 mg/L. Regulating the metabolic fluxes of the β-oxidation pathway and fatty acid elongation cycle and blocking the endogenous malonyl-CoA consumption pathway increased the titer to 113.6 ± 7.1 mg/L. Knockout of endogenous curcumin reductase (curA) and intermediate product detoxification by heterologous expression of the solvent-resistant pump (srpB) increased the titer to 137.5 ± 3.0 mg/L. A 5 L pilot-scale fermentation, using a threestage pH alternation strategy, increased the titer to 696.2 ± 20.9 mg/L, 178.5-fold higher than the highest curcumin titer from de novo biosynthesis previously reported, thereby laying the foundation for efficient biosynthesis of curcumin and its derivatives.

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Section: Discussionmentioning

confidence: 99%

Efficient De Novo Biosynthesis of Curcumin in Escherichia coli by Optimizing Pathway Modules and Increasing the Malonyl-CoA Supply

Chen,

Wang,

Wang

et al. 2023

J. Agric. Food Chem.

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“…Expression of the gene encoding type III CoaA from P. putida resulted in a 2.8-fold increase in the size of the CoA pool, with acetyl-CoA accounting for 88% of the total [ 12 ]. Increased malonyl-CoA levels were achieved by co-expressing the acetyl-CoA carboxylase (Acc) genes from Corynebacterium glutamicum along with the coaA gene, which resulted in a greater than sevenfold increase in fatty acid content [ 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

Enhanced supply of acetyl-CoA by exogenous pantothenate kinase promotes synthesis of poly(3-hydroxybutyrate)

et al. 2023

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Background Coenzyme A (CoA) is a carrier of acyl groups. This cofactor is synthesized from pantothenic acid in five steps. The phosphorylation of pantothenate is catalyzed by pantothenate kinase (CoaA), which is a key step in the CoA biosynthetic pathway. To determine whether the enhancement of the CoA biosynthetic pathway is effective for producing useful substances, the effect of elevated acetyl-CoA levels resulting from the introduction of the exogenous coaA gene on poly(3-hydroxybutyrate) [P(3HB)] synthesis was determined in Escherichia coli, which express the genes necessary for cyanobacterial polyhydroxyalkanoate synthesis (phaABEC). Results E. coli containing the coaA gene in addition to the pha genes accumulated more P(3HB) compared with the transformant containing the pha genes alone. P(3HB) production was enhanced by precursor addition, with P(3HB) content increasing from 18.4% (w/w) to 29.0% in the presence of 0.5 mM pantothenate and 16.3%–28.2% by adding 0.5 mM β-alanine. Strains expressing the exogenous coaA in the presence of precursors contained acetyl-CoA in excess of 1 nmol/mg of dry cell wt, which promoted the reaction toward P(3HB) formation. The amount of acetate exported into the medium was three times lower in the cells carrying exogenous coaA and pha genes than in the cells carrying pha genes alone. This was attributed to significantly enlarging the intracellular pool size of CoA, which is the recipient of acetic acid and is advantageous for microbial production of value-added materials. Conclusions Enhancing the CoA biosynthetic pathway with exogenous CoaA was effective at increasing P(3HB) production. Supplementing the medium with pantothenate facilitated the accumulation of P(3HB). β-Alanine was able to replace the efficacy of adding pantothenate.

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Efficient synthesis of malonyl-CoA by an acyl-CoA synthetase from Streptomyces sp.

Huang,

Yu,

Zhang

et al. 2023

Process Biochemistry

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Fatty Acid Production by Enhanced Malonyl-CoA Supply in Escherichia coli

Cited by 4 publications

References 51 publications

Efficient De Novo Biosynthesis of Curcumin in Escherichia coli by Optimizing Pathway Modules and Increasing the Malonyl-CoA Supply

Efficient De Novo Biosynthesis of Curcumin in Escherichia coli by Optimizing Pathway Modules and Increasing the Malonyl-CoA Supply

Enhanced supply of acetyl-CoA by exogenous pantothenate kinase promotes synthesis of poly(3-hydroxybutyrate)

Efficient synthesis of malonyl-CoA by an acyl-CoA synthetase from Streptomyces sp.

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