Lycopene production from glucose, fatty acid and waste cooking oil by metabolically engineered Escherichia coli

Liu, Na; Liu, Bo; Wang, Gaoyan; Soong, Ya‐Hue Valerie; Tao, Yong; Liu, Weifeng; Xie, Dongming

doi:10.1016/j.bej.2020.107488

Cited by 45 publications

(43 citation statements)

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“…Lycopene production via various metabolic engineering optimization strategies in E. coli are summarized and listed in Table 1. Removal of competing pathways ∆gdhA, ∆aceE, ∆ytjC (gpmB), ∆fdhF 18 mg/g DCW Batch shake-flask cultivations [38] Pathway balancing Combination of gene knockout and overexpression 2.5 mg/g DCW - [20] Genome-wide stoichiometric flux balance analysis; genes knockouts 6.6 mg/g DCW Shake-flask fermentation [39] Gene knockout (∆hnr, ∆yliE) -Shake-flask fermentation [40] Regulatory engineering Ntr regulon, stimulated by excess glycolytic flux through sensing of ACP 0.16 mg/L/h Shake-flask fermentation [41] Engineering of the cAMP receptor protein (CRP) 18.49 mg/g DCW Batch fermentation [42] Optimization of carbon sources Auxiliary carbon source optimization 1050 mg/L Baffled flask fermentation [12] Supplementing auxiliary carbon sources 40 mg/L/h Fed-batch culture [43] Fermentation with fatty acids or waste cooking oils 94 mg/g DCW Fed-batch fermentation [44] Optimization of fermentation High cell density fermentation 220 mg/L Batch fermentation [45] Different types of plasmid expression; optimization of fermentation conditions 67 mg/g DCW Shake-flask fermentation [46] Targeted engineering Targeted engineering; targeted proteomic and intermediate analysis 1.23 g/L Fed-batch fermentation [47] Two-dimensional search for gene targets 16 mg/g DCW Shake-flask fermentation [48] Cofactor engineering…”

Section: The Primary Biosynthetic Pathways For Lycopene Productionmentioning

confidence: 99%

“…Similarly, in another study, the MVA lower pathway was introduced into E. coli, in which glycerol was supplied as the carbon source with addition of mevalonate, and Tween 80 was added to prevent clump formation, resulting in a significant increase in lycopene production [54]. Moreover, an engineered E. coli strain introduced with the fatty acid transport system was capable of utilizing free fatty acids or waste cooking oil to produce lycopene, with the highest yield of 94 mg/g [44].…”

Section: Optimization Of Auxiliary Carbon Source and Fermentation Modesmentioning

confidence: 99%

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Metabolic Engineering Escherichia coli for the Production of Lycopene

et al. 2020

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Lycopene, a potent antioxidant, has been widely used in the fields of pharmaceuticals, nutraceuticals, and cosmetics. However, the production of lycopene extracted from natural sources is far from meeting the demand. Consequently, synthetic biology and metabolic engineering have been employed to develop microbial cell factories for lycopene production. Due to the advantages of rapid growth, complete genetic background, and a reliable genetic operation technique, Escherichia coli has become the preferred host cell for microbial biochemicals production. In this review, the recent advances in biological lycopene production using engineered E. coli strains are summarized: First, modification of the endogenous MEP pathway and introduction of the heterogeneous MVA pathway for lycopene production are outlined. Second, the common challenges and strategies for lycopene biosynthesis are also presented, such as the optimization of other metabolic pathways, modulation of regulatory networks, and optimization of auxiliary carbon sources and the fermentation process. Finally, the future prospects for the improvement of lycopene biosynthesis are also discussed.

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Section: The Primary Biosynthetic Pathways For Lycopene Productionmentioning

confidence: 99%

Section: Optimization Of Auxiliary Carbon Source and Fermentation Modesmentioning

confidence: 99%

Metabolic Engineering Escherichia coli for the Production of Lycopene

et al. 2020

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“…For example, when obtained from palm industry byproducts, the average carbon price per ton of palmitic acid is about $35 per ton of C (calculated from $570 per ton of palmitic acid extract), which is much lower than the average carbon price for glucose ($46 per ton of C, calculated from $275 per ton of glucose) [27]. In previous studies, we have successfully developed efficient routes to produce target chemicals, such as 3-hydroxypropionic acid and lycopene, in high yields from fatty acids [28,29].…”

Section: Introductionmentioning

confidence: 99%

Efficient bioconversion of raspberry ketone in Escherichia coli using fatty acids feedstocks

et al. 2021

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Background Phenylpropanoid including raspberry ketone, is a kind of important natural plant product and widely used in pharmaceuticals, chemicals, cosmetics, and healthcare products. Bioproduction of phenylpropanoid in Escherichia coli and other microbial cell factories is an attractive approach considering the low phenylpropanoid contents in plants. However, it is usually difficult to produce high titer phenylpropanoid production when fermentation using glucose as carbon source. Developing novel bioprocess using alternative sources might provide a solution to this problem. In this study, typical phenylpropanoid raspberry ketone was used as the target product to develop a biosynthesis pathway for phenylpropanoid production from fatty acids, a promising alternative low-cost feedstock. Results A raspberry ketone biosynthesis module was developed and optimized by introducing 4-coumarate-CoA ligase (4CL), benzalacetone synthase (BAS), and raspberry ketone reductase (RZS) in Escherichia coli strains CR1–CR4. Then strain CR5 was developed by introducing raspberry ketone biosynthesis module into a fatty acids-utilization chassis FA09 to achieve production of raspberry ketone from fatty acids feedstock. However, the production of raspberry ketone was still limited by the low biomass and unable to substantiate whole-cell bioconversion process. Thus, a process by coordinately using fatty-acids and glycerol was developed. In addition, we systematically screened and optimized fatty acids-response promoters. The optimized promoter Pfrd3 was then successfully used for the efficient expression of key enzymes of raspberry ketone biosynthesis module during bioconversion from fatty acids. The final engineered strain CR8 could efficiently produce raspberry ketone repeatedly using bioconversion from fatty acids feedstock strategy, and was able to produce raspberry ketone to a concentration of 180.94 mg/L from soybean oil in a 1-L fermentation process. Conclusion Metabolically engineered Escherichia coli strains were successfully developed for raspberry ketone production from fatty acids using several strategies, including optimization of bioconversion process and fine-tuning key enzyme expression. This study provides an essential reference to establish the low-cost biological manufacture of phenylpropanoids compounds.

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“…For example, when obtained from palm industry byproducts, the average carbon price per ton of palmitic acid is about $35 per ton of C (calculated from $570 per ton of palmitic acid extract), which is much lower than the average carbon price for glucose ($46 per ton of C, calculated from $275 per ton of glucose) [27]. In previous studies, we have successfully developed e cient routes to produce target chemicals, such as 3-hydroxypropionic acid and lycopene, in high yields from fatty acids [28,29].…”

Section: Introductionmentioning

confidence: 99%

Efficient Bioconversion of Raspberry Ketone in Escherichia Coli Using Fatty Acids Feedstocks

Chen

Liu

Bao

et al. 2020

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BackgroundPhenylpropanoid including raspberry ketone, is a kind of important natural plant product and widely used in pharmaceuticals, chemicals, cosmetics, and healthcare products. Bioproduction of phenylpropanoid in Escherichia coli and other microbial cell factories is an attractable approach considering the low phenylpropanoid contents in plants. However, it is usually difficult to produce high titer phenylpropanoid production when fermentation using glucose as carbon source. Developing novel bioprocess using alternative sources might provide a solution to this problem. In this study, typical phenylpropanoid raspberry ketone was used as the target product to develop a biosynthesis pathway for phenylpropanoid production from fatty acids, a promising alternative low-cost feedstock. ResultsA raspberry ketone biosynthesis module was developed and optimized by introducing 4-coumarate-CoA ligase (4CL), benzalacetone synthase (BAS), and raspberry ketone reductase (RZS) in Escherichia coli strains CR1-CR4. Then strain CR5 was developed by introducing raspberry ketone biosynthesis module into a fatty acids-utilization chassis FA09 to achieve production of raspberry ketone from fatty acids feedstock. However, the production of raspberry ketone was still limited by the low biomass and unable to substantiate whole-cell bioconversion process. Thus, a process by coordinately using fatty-acids and glycerol was developed. In addition, we systematically screened and optimized fatty acids-response promoters. The optimized promoter Pfrd3 was then successfully used for the efficient expression of key enzymes of raspberry ketone biosynthesis module during bioconversion from fatty acids. The final engineered strain CR8 could efficiently produce raspberry ketone repeatedly using bioconversion from fatty acids feedstock strategy, and about 291.3 mg/L raspberry ketone was produced.ConclusionMetabolically engineered Escherichia coli strains were successfully developed for raspberry ketone production from fatty acids using several strategies, including optimization of bioconversion process and fine-tuning key enzyme expression. This study provides an essential reference to establish the low-cost biological manufacture of phenylpropanoids compounds.

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Lycopene production from glucose, fatty acid and waste cooking oil by metabolically engineered Escherichia coli

Cited by 45 publications

References 38 publications

Metabolic Engineering Escherichia coli for the Production of Lycopene

Metabolic Engineering Escherichia coli for the Production of Lycopene

Efficient bioconversion of raspberry ketone in Escherichia coli using fatty acids feedstocks

Efficient Bioconversion of Raspberry Ketone in Escherichia Coli Using Fatty Acids Feedstocks

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