Search: onr:"swepub:oai:research.chalmers.se:04b19fc9-123a-4c2f-81c2-5e3f7f149c68" >
De novo biosynthesi...
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Liu, Quanli,1988Chalmers tekniska högskola,Chalmers University of Technology,Novo Nordisk Fonden,Novo Nordisk Foundation
(author)
De novo biosynthesis of bioactive isoflavonoids by engineered yeast cell factories
- Article/chapterEnglish2021
Publisher, publication year, extent ...
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2021-10-19
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Springer Science and Business Media LLC,2021
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electronicrdacarrier
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LIBRIS-ID:oai:research.chalmers.se:04b19fc9-123a-4c2f-81c2-5e3f7f149c68
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https://doi.org/10.1038/s41467-021-26361-1DOI
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https://research.chalmers.se/publication/526808URI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:art swepub-publicationtype
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Subject category:ref swepub-contenttype
Notes
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Isoflavonoids comprise a class of plant natural products with great nutraceutical, pharmaceutical and agricultural significance. Their low abundance in nature and structural complexity however hampers access to these phytochemicals through traditional crop-based manufacturing or chemical synthesis. Microbial bioproduction therefore represents an attractive alternative. Here, we engineer the metabolism of Saccharomyces cerevisiae to become a platform for efficient production of daidzein, a core chemical scaffold for isoflavonoid biosynthesis, and demonstrate its application towards producing bioactive glucosides from glucose, following the screening-reconstruction-application engineering framework. First, we rebuild daidzein biosynthesis in yeast and its production is then improved by 94-fold through screening biosynthetic enzymes, identifying rate-limiting steps, implementing dynamic control, engineering substrate trafficking and fine-tuning competing metabolic processes. The optimized strain produces up to 85.4 mg L−1 of daidzein and introducing plant glycosyltransferases in this strain results in production of bioactive puerarin (72.8 mg L−1) and daidzin (73.2 mg L−1). Our work provides a promising step towards developing synthetic yeast cell factories for de novo biosynthesis of value-added isoflavonoids and the multi-phased framework may be extended to engineer pathways of complex natural products in other microbial hosts.
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Liu, Yi,1986Novo Nordisk Fonden,Novo Nordisk Foundation,Chalmers tekniska högskola,Chalmers University of Technology(Swepub:cth)liuyi
(author)
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Li, Gang,1991Chalmers tekniska högskola,Chalmers University of Technology,Novo Nordisk Fonden,Novo Nordisk Foundation(Swepub:cth)gangl
(author)
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Savolainen, Otto,1982Chalmers tekniska högskola,Chalmers University of Technology,Itä-Suomen Yliopisto,University of Eastern Finland(Swepub:cth)sotto
(author)
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Chen, Yun,1978Novo Nordisk Fonden,Novo Nordisk Foundation,Chalmers tekniska högskola,Chalmers University of Technology(Swepub:cth)yunc
(author)
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Nielsen, Jens B,1962Novo Nordisk Fonden,Novo Nordisk Foundation,Danmarks Tekniske Universitet,Technical University of Denmark,BioInnovation Institute (BII),Chalmers tekniska högskola,Chalmers University of Technology(Swepub:cth)nielsenj
(author)
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Chalmers tekniska högskolaNovo Nordisk Fonden
(creator_code:org_t)
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In:Nature Communications: Springer Science and Business Media LLC12:12041-17232041-1723
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