Gene Source Screening as a Tool for Naringenin Production in Engineered <i>Saccharomyces cerevisiae</i>

Mark, Rita; Lyu, Xiaomei; Ng, Kuan Rei; Chen, Wei Ning

doi:10.1021/acsomega.9b00364

Cited by 22 publications

(21 citation statements)

References 36 publications

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“…Naringenin production is mainly through plant extraction, with certain limitations, such as the source of plant materials, the stability of extraction methods, and harmful materials produced ( Zang et al, 2019 ). In addition, the metabolic synthesis of naringenin has been widely studied ( Koopman et al, 2012 ; Liu et al, 2017 ; Ibdah et al, 2018 ; Mark et al, 2019 ; Zhang et al, 2021 ). 4-coumarin-CoA ligase (4CL), CHS, and CHI are pivotal in synthesizing naringenin.…”

Section: Introductionmentioning

confidence: 99%

AfCHIL, a Type IV Chalcone Isomerase, Enhances the Biosynthesis of Naringenin in Metabolic Engineering

Lan

Xing

et al. 2022

Front. Plant Sci.

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Naringenin is an essential precursor for all flavonoids, and effectively promoting naringenin production is crucial in metabolic engineering. The interaction between plant metabolic enzymes ensures metabolic flux. The effect can effectively improve the natural product synthesis of engineering microbial systems. In this study, chalcone isomerase genes in Allium fistulosum have been identified. The expression of AfCHIL is closely related to the accumulation of anthocyanins, and the expression of AfCHIL and AfCHS was highly synchronized. Yeast two-hybrid and firefly luciferase complementation imaging assay further confirmed AfCHIL physically interacted with AfCHS/AfCHI. The bioconversion experiment confirmed that AfCHIL reduced the derailment produced by AfCHS and increased the yield of naringenin. In addition, a system of biosynthesis naringenin involved in AfCHS was constructed, and these results suggested that the potential function between CHS with CHIL advanced naringenin production effectively. In conclusion, this study illustrated the function of AfCHIs in Allium fistulosum and provided new insight into improving the synthesis efficiency of naringenin.

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Section: Introductionmentioning

confidence: 99%

AfCHIL, a Type IV Chalcone Isomerase, Enhances the Biosynthesis of Naringenin in Metabolic Engineering

Lan

Xing

et al. 2022

Front. Plant Sci.

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“…Both enzyme variants and gene expression levels of the essential genes were engineered to address this challenge. For example, the 4CL gene from Medicago truncatula and CHS gene from Vitis vinifera led to the highest naringenin production among various combinations (Mark et al, 2019). TALs and CHSs from different organisms can also lead to optimized flavonoid production (Santos et al, 2011;Tong et al, 2022).…”

Section: Gene Selection and Expression Level Optimizationmentioning

confidence: 99%

Engineered biosynthesis of plant polyketides by type III polyketide synthases in microorganisms

Liu

2022

Front. Bioeng. Biotechnol.

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Plant specialized metabolites occupy unique therapeutic niches in human medicine. A large family of plant specialized metabolites, namely plant polyketides, exhibit diverse and remarkable pharmaceutical properties and thereby great biomanufacturing potential. A growing body of studies has focused on plant polyketide synthesis using plant type III polyketide synthases (PKSs), such as flavonoids, stilbenes, benzalacetones, curcuminoids, chromones, acridones, xanthones, and pyrones. Microbial expression of plant type III PKSs and related biosynthetic pathways in workhorse microorganisms, such as Saccharomyces cerevisiae, Escherichia coli, and Yarrowia lipolytica, have led to the complete biosynthesis of multiple plant polyketides, such as flavonoids and stilbenes, from simple carbohydrates using different metabolic engineering approaches. Additionally, advanced biosynthesis techniques led to the biosynthesis of novel and complex plant polyketides synthesized by diversified type III PKSs. This review will summarize efforts in the past 10 years in type III PKS-catalyzed natural product biosynthesis in microorganisms, especially the complete biosynthesis strategies and achievements.

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“…2 ). In addition, the screening of gene sources other than A. thaliana would be also effective for increasing the naringenin productivity ( Mark et al., 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Synthetic production of prenylated naringenins in yeast using promiscuous microbial prenyltransferases

Isogai

Okahashi

Asama

et al. 2021

Metabolic Engineering Communications

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Reconstitution of prenylflavonoids using the flavonoid biosynthetic pathway and prenyltransferases (PTs) in microbes can be a promising attractive alternative to plant-based production or chemical synthesis. Here, we demonstrate that promiscuous microbial PTs can be a substitute for regiospecific but mostly unidentified botanical PTs. To test the prenylations of naringenin, we constructed a yeast strain capable of producing naringenin from l -phenylalanine by genomic integration of six exogenous genes encoding components of the naringenin biosynthetic pathway. Using this platform strain, various microbial PTs were tested for prenylnaringenin production. In vitro screening demonstrated that the fungal AnaPT (a member of the tryptophan dimethylallyltransferase family) specifically catalyzed C-3′ prenylation of naringenin, whereas SfN8DT-1, a botanical PT, specifically catalyzed C-8 prenylation. In vivo , the naringenin-producing strain expressing the microbial AnaPT exhibited heterologous microbial production of 3′-prenylnaringenin (3′-PN), in contrast to the previously reported in vivo production of 8-prenylnaringenin (8-PN) using the botanical SfN8DT-1. These findings provide strategies towards expanding the production of a variety of prenylated compounds, including well-known prenylnaringenins and novel prenylflavonoids. These results also suggest the opportunity for substituting botanical PTs, both known and unidentified, that display relatively strict regiospecificity of the prenyl group transfer.

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Gene Source Screening as a Tool for Naringenin Production in Engineered Saccharomyces cerevisiae

Cited by 22 publications

References 36 publications

AfCHIL, a Type IV Chalcone Isomerase, Enhances the Biosynthesis of Naringenin in Metabolic Engineering

AfCHIL, a Type IV Chalcone Isomerase, Enhances the Biosynthesis of Naringenin in Metabolic Engineering

Engineered biosynthesis of plant polyketides by type III polyketide synthases in microorganisms

Synthetic production of prenylated naringenins in yeast using promiscuous microbial prenyltransferases

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