Modular Engineering of <i>Saccharomyces cerevisiae</i> for De Novo Biosynthesis of Genistein

Genistein, a nutraceutical isoflavone, has various pharmaceutical and biological activities which benefit human health via soy-containing food intake. This study aimed to construct <i>Saccharomyces cerevisiae</i> to produce genistein from sugar via a modular engineering strategy. In the...

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Main Authors: Yonghui Meng, Xue Liu, Lijuan Zhang, Guang-Rong Zhao
Format: Article
Language:English
Published: MDPI AG 2022-07-01
Series:Microorganisms
Subjects:
Online Access:https://www.mdpi.com/2076-2607/10/7/1402
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author Yonghui Meng
Xue Liu
Lijuan Zhang
Guang-Rong Zhao
author_facet Yonghui Meng
Xue Liu
Lijuan Zhang
Guang-Rong Zhao
author_sort Yonghui Meng
collection DOAJ
description Genistein, a nutraceutical isoflavone, has various pharmaceutical and biological activities which benefit human health via soy-containing food intake. This study aimed to construct <i>Saccharomyces cerevisiae</i> to produce genistein from sugar via a modular engineering strategy. In the midstream module, various sources of chalcone synthases and chalcone isomerase-like proteins were tested which enhanced the naringenin production from <i>p</i>-coumaric acid by decreasing the formation of the byproduct. The upstream module was reshaped to enhance the metabolic flux to <i>p</i>-coumaric acid from glucose by overexpressing the genes in the tyrosine biosynthetic pathway and deleting the competing genes. The downstream module was rebuilt to produce genistein from naringenin by pairing various isoflavone synthases and cytochrome P450 reductases. The optimal pair was used for the de novo biosynthesis of genistein with a titer of 31.02 mg/L from sucrose at 25 °C. This is the first report on the de novo biosynthesis of genistein in engineered <i>S. cerevisiae</i> to date. This work shows promising potential for producing flavonoids and isoflavonoids by modular metabolic engineering.
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spelling doaj.art-bcd49db9a3674507b4ba2701fec6ab632023-11-30T21:30:45ZengMDPI AGMicroorganisms2076-26072022-07-01107140210.3390/microorganisms10071402Modular Engineering of <i>Saccharomyces cerevisiae</i> for De Novo Biosynthesis of GenisteinYonghui Meng0Xue Liu1Lijuan Zhang2Guang-Rong Zhao3Frontiers Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (Ministry of Education), School of Chemical Engineering and Technology, Tianjin University, Yaguan Road 135, Jinnan District, Tianjin 300350, ChinaFrontiers Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (Ministry of Education), School of Chemical Engineering and Technology, Tianjin University, Yaguan Road 135, Jinnan District, Tianjin 300350, ChinaFrontiers Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (Ministry of Education), School of Chemical Engineering and Technology, Tianjin University, Yaguan Road 135, Jinnan District, Tianjin 300350, ChinaFrontiers Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (Ministry of Education), School of Chemical Engineering and Technology, Tianjin University, Yaguan Road 135, Jinnan District, Tianjin 300350, ChinaGenistein, a nutraceutical isoflavone, has various pharmaceutical and biological activities which benefit human health via soy-containing food intake. This study aimed to construct <i>Saccharomyces cerevisiae</i> to produce genistein from sugar via a modular engineering strategy. In the midstream module, various sources of chalcone synthases and chalcone isomerase-like proteins were tested which enhanced the naringenin production from <i>p</i>-coumaric acid by decreasing the formation of the byproduct. The upstream module was reshaped to enhance the metabolic flux to <i>p</i>-coumaric acid from glucose by overexpressing the genes in the tyrosine biosynthetic pathway and deleting the competing genes. The downstream module was rebuilt to produce genistein from naringenin by pairing various isoflavone synthases and cytochrome P450 reductases. The optimal pair was used for the de novo biosynthesis of genistein with a titer of 31.02 mg/L from sucrose at 25 °C. This is the first report on the de novo biosynthesis of genistein in engineered <i>S. cerevisiae</i> to date. This work shows promising potential for producing flavonoids and isoflavonoids by modular metabolic engineering.https://www.mdpi.com/2076-2607/10/7/1402genisteinmodular engineering<i>Saccharomyces cerevisiae</i>metabolic engineeringsynthetic biology
spellingShingle Yonghui Meng
Xue Liu
Lijuan Zhang
Guang-Rong Zhao
Modular Engineering of <i>Saccharomyces cerevisiae</i> for De Novo Biosynthesis of Genistein
Microorganisms
genistein
modular engineering
<i>Saccharomyces cerevisiae</i>
metabolic engineering
synthetic biology
title Modular Engineering of <i>Saccharomyces cerevisiae</i> for De Novo Biosynthesis of Genistein
title_full Modular Engineering of <i>Saccharomyces cerevisiae</i> for De Novo Biosynthesis of Genistein
title_fullStr Modular Engineering of <i>Saccharomyces cerevisiae</i> for De Novo Biosynthesis of Genistein
title_full_unstemmed Modular Engineering of <i>Saccharomyces cerevisiae</i> for De Novo Biosynthesis of Genistein
title_short Modular Engineering of <i>Saccharomyces cerevisiae</i> for De Novo Biosynthesis of Genistein
title_sort modular engineering of i saccharomyces cerevisiae i for de novo biosynthesis of genistein
topic genistein
modular engineering
<i>Saccharomyces cerevisiae</i>
metabolic engineering
synthetic biology
url https://www.mdpi.com/2076-2607/10/7/1402
work_keys_str_mv AT yonghuimeng modularengineeringofisaccharomycescerevisiaeifordenovobiosynthesisofgenistein
AT xueliu modularengineeringofisaccharomycescerevisiaeifordenovobiosynthesisofgenistein
AT lijuanzhang modularengineeringofisaccharomycescerevisiaeifordenovobiosynthesisofgenistein
AT guangrongzhao modularengineeringofisaccharomycescerevisiaeifordenovobiosynthesisofgenistein