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De Novo Biosynthesis of Vindoline and Catharanthine in Saccharomyces cerevisiae

Vinblastine has been used clinically as one of the most potent therapeutics for the treatment of several types of cancer. However, the traditional plant extraction method suffers from unreliable supply, low abundance, and extremely high cost. Here, we use synthetic biology approach to engineer Sacch...

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Autores principales: Gao, Di, Liu, Tengfei, Gao, Jucan, Xu, Junhao, Gou, Yuanwei, Pan, Yingjia, Li, Dongfang, Ye, Cuifang, Pan, Ronghui, Huang, Lei, Xu, Zhinan, Lian, Jiazhang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AAAS 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10593122/
https://www.ncbi.nlm.nih.gov/pubmed/37905202
http://dx.doi.org/10.34133/bdr.0002
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author Gao, Di
Liu, Tengfei
Gao, Jucan
Xu, Junhao
Gou, Yuanwei
Pan, Yingjia
Li, Dongfang
Ye, Cuifang
Pan, Ronghui
Huang, Lei
Xu, Zhinan
Lian, Jiazhang
author_facet Gao, Di
Liu, Tengfei
Gao, Jucan
Xu, Junhao
Gou, Yuanwei
Pan, Yingjia
Li, Dongfang
Ye, Cuifang
Pan, Ronghui
Huang, Lei
Xu, Zhinan
Lian, Jiazhang
author_sort Gao, Di
collection PubMed
description Vinblastine has been used clinically as one of the most potent therapeutics for the treatment of several types of cancer. However, the traditional plant extraction method suffers from unreliable supply, low abundance, and extremely high cost. Here, we use synthetic biology approach to engineer Saccharomyces cerevisiae for de novo biosynthesis of vindoline and catharanthine, which can be coupled chemically or biologically to vinblastine. On the basis of a platform strain with sufficient supply of precursors and cofactors for biosynthesis, we reconstituted, debottlenecked, and optimized the biosynthetic pathways for the production of vindoline and catharanthine. The vindoline biosynthetic pathway represents one of the most complicated pathways ever reconstituted in microbial cell factories. Using shake flask fermentation, our engineered yeast strains were able to produce catharanthine and vindoline at a titer of 527.1 and 305.1 μg·liter(−1), respectively, without accumulating detectable amount of pathway intermediates. This study establishes a representative example for the production of valuable plant natural products in yeast.
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spelling pubmed-105931222023-10-30 De Novo Biosynthesis of Vindoline and Catharanthine in Saccharomyces cerevisiae Gao, Di Liu, Tengfei Gao, Jucan Xu, Junhao Gou, Yuanwei Pan, Yingjia Li, Dongfang Ye, Cuifang Pan, Ronghui Huang, Lei Xu, Zhinan Lian, Jiazhang Biodes Res Research Article Vinblastine has been used clinically as one of the most potent therapeutics for the treatment of several types of cancer. However, the traditional plant extraction method suffers from unreliable supply, low abundance, and extremely high cost. Here, we use synthetic biology approach to engineer Saccharomyces cerevisiae for de novo biosynthesis of vindoline and catharanthine, which can be coupled chemically or biologically to vinblastine. On the basis of a platform strain with sufficient supply of precursors and cofactors for biosynthesis, we reconstituted, debottlenecked, and optimized the biosynthetic pathways for the production of vindoline and catharanthine. The vindoline biosynthetic pathway represents one of the most complicated pathways ever reconstituted in microbial cell factories. Using shake flask fermentation, our engineered yeast strains were able to produce catharanthine and vindoline at a titer of 527.1 and 305.1 μg·liter(−1), respectively, without accumulating detectable amount of pathway intermediates. This study establishes a representative example for the production of valuable plant natural products in yeast. AAAS 2022-12-26 /pmc/articles/PMC10593122/ /pubmed/37905202 http://dx.doi.org/10.34133/bdr.0002 Text en Copyright © 2022 Di Gao et al. https://creativecommons.org/licenses/by/4.0/Exclusive licensee Nanjing Agricultural University. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY 4.0) (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Gao, Di
Liu, Tengfei
Gao, Jucan
Xu, Junhao
Gou, Yuanwei
Pan, Yingjia
Li, Dongfang
Ye, Cuifang
Pan, Ronghui
Huang, Lei
Xu, Zhinan
Lian, Jiazhang
De Novo Biosynthesis of Vindoline and Catharanthine in Saccharomyces cerevisiae
title De Novo Biosynthesis of Vindoline and Catharanthine in Saccharomyces cerevisiae
title_full De Novo Biosynthesis of Vindoline and Catharanthine in Saccharomyces cerevisiae
title_fullStr De Novo Biosynthesis of Vindoline and Catharanthine in Saccharomyces cerevisiae
title_full_unstemmed De Novo Biosynthesis of Vindoline and Catharanthine in Saccharomyces cerevisiae
title_short De Novo Biosynthesis of Vindoline and Catharanthine in Saccharomyces cerevisiae
title_sort de novo biosynthesis of vindoline and catharanthine in saccharomyces cerevisiae
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10593122/
https://www.ncbi.nlm.nih.gov/pubmed/37905202
http://dx.doi.org/10.34133/bdr.0002
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