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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MDPI AG
2022-07-01
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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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language | English |
last_indexed | 2024-03-09T13:20:44Z |
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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 |