Microbial cell factories for the production of flavonoids–barriers and opportunities

Li, Hongbiao; Lyv, Yunbin; Zhou, Shenghu; Yu, Shiqin; Zhou, Jingwen

doi:10.1016/j.biortech.2022.127538

Cited by 25 publications

(15 citation statements)

References 87 publications

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“…Particularly, the At C4H employed in resveratrol synthesis pathway is a membrane-associated plant-derived P450 enzyme, whose heterologous expression may suffer from insufficient cofactor NADPH supply [ 24 ]. Additionally, as a heme-thiolate protein, the plant-derived cytochrome P450 monooxygenase At C4H also requires a cytochrome P450 redox partner [ 24 , 25 ]. It has been reported that the decline in the catalytic activity of P450 is caused by inadequate and inefficient cofactors, and it would lead to a limitation of resveratrol overproduction [ 7 , 19 ].…”

Section: Resultsmentioning

confidence: 99%

“…The heterologous expression of a plant originated pathway may function sub-optimally due to the unsuitable cofactor as in the case of microbial production of resveratrol [ 5 ]. Particularly, the At C4H employed in resveratrol synthesis pathway is a membrane-associated plant-derived P450 enzyme, whose heterologous expression may suffer from insufficient cofactor NADPH supply [ 24 ]. Additionally, as a heme-thiolate protein, the plant-derived cytochrome P450 monooxygenase At C4H also requires a cytochrome P450 redox partner [ 24 , 25 ].…”

Section: Resultsmentioning

confidence: 99%

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Metabolic engineering of Rhodotorula toruloides for resveratrol production

et al. 2022

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Background Resveratrol is a plant-derived phenylpropanoid with diverse biological activities and pharmacological applications. Plant-based extraction could not satisfy ever-increasing market demand, while chemical synthesis is impeded by the existence of toxic impurities. Microbial production of resveratrol offers a promising alternative to plant- and chemical-based processes. The non-conventional oleaginous yeast Rhodotorula toruloides is a potential workhorse for the production of resveratrol that endowed with an efficient and intrinsic bifunctional phenylalanine/tyrosine ammonia-lyase (RtPAL) and malonyl-CoA pool, which may facilitate the resveratrol synthesis when properly rewired. Results Resveratrol showed substantial stability and would not affect the R. toruloides growth during the yeast cultivation in flasks. The heterologus resveratrol biosynthesis pathway was established by introducing the 4-coumaroyl-CoA ligase (At4CL), and the stilbene synthase (VlSTS) from Arabidopsis thaliana and Vitis labrusca, respectively. Next, The resveratrol production was increased by 634% through employing the cinnamate-4-hydroxylase from A. thaliana (AtC4H), the fused protein At4CL::VlSTS, the cytochrome P450 reductase 2 from A. thaliana (AtATR2) and the endogenous cytochrome B5 of R. toruloides (RtCYB5). Then, the related endogenous pathways were optimized to affect a further 60% increase. Finally, the engineered strain produced a maximum titer of 125.2 mg/L resveratrol in YPD medium. Conclusion The non-conventional oleaginous yeast R. toruloides was engineered for the first time to produce resveratrol. Protein fusion, co-factor channeling, and ARO4 and ARO7 overexpression were efficient for improving resveratrol production. The results demonstrated the potential of R. toruloides for resveratrol and other phenylpropanoids production.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Metabolic engineering of Rhodotorula toruloides for resveratrol production

et al. 2022

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“…In addition to the physiological and morphogenetic processes that take place during seed germination (1), changes in the synthesis and accumulation of specialized metabolites also can happen (2). These metabolites play important physiological roles in germinating seeds (3) and have agronomic (4,5) and pharmaceutical importance (6,7). For Paseolus vulgaris, one of the most economically important edible species of Fabaceae, in whose seeds, phenolics are the predominant bioactive compounds (8), the deter-mination of the changes in its composition could support the understanding of its germination mechanism, as well as the development of markers for the selection of genotypes accumulating high levels of phenolics and the evaluation of the potential of common bean sprouts as a functional food.…”

Section: Introductionmentioning

confidence: 99%

Variation of the phenolic composition and a-glucosidase inhibition potential of seeds, soaked seeds, and sprouts of four wild forms and four varieties of common bean (Phaseolus vulgaris)

Almaraz-Abarca

Ayala-Chaidez²,

Wallander-Compeán³

et al. 2023

Plant Sci. Today

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The determination of the changes in the composition of bioactive phenolic compounds of germinating seeds which accumulate high levels of these compounds could contribute to the understanding of the germination mechanism and the development of markers for the selection of plant genotypes. In the current study, the changes in the phenolic composition and a-glucosidase inhibition activity, taking place during the germination of four wild forms and four varieties of common bean (Phaseolus vulgaris L.) from Durango Mexico, were determined. A total of 66 phenolic compounds (19 phenolic acids, 18 isoflavones, 18 flavonol glycosides, 3 flavonol aglycones, 3 flavones, 2 dihydroflavonoids, 2 chalcones and one non-identified type) were found by HPLC-DAD, which were differentially accumulated by the seeds, 24 h-soaked seeds, and 4 day-sprouts of each genotype. The accumulation of the flavonol aglycones, myricetin, quercetin and kaempferol was distinctive of the wild seeds. Soaking not only caused leaching and degradation but also triggered the synthesis of new phenolic compounds whereas germination diversified the composition of isoflavones and flavonol glycosides. The seeds of all genotypes analyzed were important inhibitors of a-glucosidase, improving their potential after soaking and germination. The results suggested that the structure rather than the concentration of the flavonoids and phenolic acids determined the inhibitory potential of a-glucosidase of samples. The principal component analysis and cluster analysis revealed HPLC-DAD phenolic profiles as genotype-specific chemomarkers at any of the states (seeds, soaked seeds, and sprouts). The results have wide implications on agronomy and food quality.

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“…Only a few 4CLs, including Sc4CL, At4CL1, Pc4CL and Ptr4CL5, were used for the biosynthesis of trans -cinnamic acid derivatives [ 40 ]. However, their results were poor [ 41 ]. Our results showed that the wood-derived gene Ptr4CL4 is more efficient than the other genes for pinosylvin production.…”

Section: Resultsmentioning

confidence: 99%

Efficient biosynthesis of pinosylvin from lignin-derived cinnamic acid by metabolic engineering of Escherichia coli

Zhang

Zou

et al. 2022

Biotechnol Biofuels

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Background The conversion of lignin-derived aromatic monomers into valuable chemicals has promising potential to improve the economic competitiveness of biomass biorefineries. Pinosylvin is an attractive pharmaceutical with multiple promising biological activities. Results Herein, Escherichia coli was engineered to convert the lignin-derived standard model monomer cinnamic acid into pinosylvin by introducing two novel enzymes from the wood plant: stilbene synthase from Pinus pinea (PpSTS) and 4-Coumarate-CoA ligase from Populus trichocarpa (Ptr4CL4). The expression of Ptr4CL4 drastically improved the production of pinosylvin (42.5 ± 1.1 mg/L), achieving values 15.7-fold higher than that of Ptr4CL5 (another 4-Coumarate-CoA ligase from Populus trichocarpa) in the absence of cerulenin. By adjusting the expression strategy, the optimized engineered strain produced pinosylvin at 153.7 ± 2.2 mg/L with an extremely high yield of 1.20 ± 0.02 mg/mg cinnamic acid in the presence of cerulenin, which is 83.9% ± 1.17 of the theoretical yield. This is the highest reported pinosylvin yield directly from cinnamic acid to date. Conclusion Our work highlights the feasibility of microbial production of pinosylvin from cinnamic acid and paves the way for converting lignin-related aromatics to valuable chemicals.

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Microbial cell factories for the production of flavonoids–barriers and opportunities

Cited by 25 publications

References 87 publications

Metabolic engineering of Rhodotorula toruloides for resveratrol production

Metabolic engineering of Rhodotorula toruloides for resveratrol production

Variation of the phenolic composition and a-glucosidase inhibition potential of seeds, soaked seeds, and sprouts of four wild forms and four varieties of common bean (Phaseolus vulgaris)

Efficient biosynthesis of pinosylvin from lignin-derived cinnamic acid by metabolic engineering of Escherichia coli

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