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De novo biosynthesi...
De novo biosynthesis of bioactive isoflavonoids by engineered yeast cell factories
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- Liu, Quanli, 1988 (author)
- Chalmers tekniska högskola,Chalmers University of Technology,Novo Nordisk Fonden,Novo Nordisk Foundation
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- Liu, Yi, 1986 (author)
- Novo Nordisk Fonden,Novo Nordisk Foundation,Chalmers tekniska högskola,Chalmers University of Technology
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- Li, Gang, 1991 (author)
- Chalmers tekniska högskola,Chalmers University of Technology,Novo Nordisk Fonden,Novo Nordisk Foundation
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- Savolainen, Otto, 1982 (author)
- Chalmers tekniska högskola,Chalmers University of Technology,Itä-Suomen Yliopisto,University of Eastern Finland
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- Chen, Yun, 1978 (author)
- Novo Nordisk Fonden,Novo Nordisk Foundation,Chalmers tekniska högskola,Chalmers University of Technology
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- Nielsen, Jens B, 1962 (author)
- Novo Nordisk Fonden,Novo Nordisk Foundation,Danmarks Tekniske Universitet,Technical University of Denmark,BioInnovation Institute (BII),Chalmers tekniska högskola,Chalmers University of Technology
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(creator_code:org_t)
- 2021-10-19
- 2021
- English.
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723 .- 2041-1723. ; 12:1
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Abstract
Subject headings
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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.
Subject headings
- TEKNIK OCH TEKNOLOGIER -- Maskinteknik -- Produktionsteknik, arbetsvetenskap och ergonomi (hsv//swe)
- ENGINEERING AND TECHNOLOGY -- Mechanical Engineering -- Production Engineering, Human Work Science and Ergonomics (hsv//eng)
- TEKNIK OCH TEKNOLOGIER -- Maskinteknik -- Annan maskinteknik (hsv//swe)
- ENGINEERING AND TECHNOLOGY -- Mechanical Engineering -- Other Mechanical Engineering (hsv//eng)
- TEKNIK OCH TEKNOLOGIER -- Industriell bioteknik -- Biokatalys och enzymteknik (hsv//swe)
- ENGINEERING AND TECHNOLOGY -- Industrial Biotechnology -- Biocatalysis and Enzyme Technology (hsv//eng)
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Liu, Quanli, 198 ...
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Liu, Yi, 1986
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Li, Gang, 1991
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Savolainen, Otto ...
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Chen, Yun, 1978
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Nielsen, Jens B, ...
- About the subject
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- ENGINEERING AND TECHNOLOGY
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ENGINEERING AND ...
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and Mechanical Engin ...
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and Production Engin ...
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- ENGINEERING AND TECHNOLOGY
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ENGINEERING AND ...
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and Mechanical Engin ...
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and Other Mechanical ...
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- ENGINEERING AND TECHNOLOGY
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ENGINEERING AND ...
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and Industrial Biote ...
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and Biocatalysis and ...
- Articles in the publication
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Nature Communica ...
- By the university
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Chalmers University of Technology