De novo biosynthesis of bioactive isoflavonoids by engineered yeast cell factories
Artikel i vetenskaplig tidskrift, 2021

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.

Författare

Quanli Liu

Novo Nordisk Foundation Center for Biosustainability

Chalmers, Biologi och bioteknik, Systembiologi

Yi Liu

Chalmers, Biologi och bioteknik, Systembiologi

Novo Nordisk Foundation Center for Biosustainability

Gang Li

Chalmers, Biologi och bioteknik, Systembiologi

Novo Nordisk Foundation Center for Biosustainability

Otto Savolainen

Itä-Suomen Yliopisto

Chalmers, Biologi och bioteknik, Systembiologi, CMSI

Yun Chen

Chalmers, Biologi och bioteknik, Systembiologi

Novo Nordisk Foundation Center for Biosustainability

Jens B Nielsen

BioInnovation Institute

Danmarks Tekniske Universitet (DTU)

Novo Nordisk Foundation Center for Biosustainability

Chalmers, Biologi och bioteknik, Systembiologi

Nature Communications

2041-1723 (ISSN)

Vol. 12 1 6085

Ämneskategorier

Produktionsteknik, arbetsvetenskap och ergonomi

Annan maskinteknik

Biokatalys och enzymteknik

DOI

10.1038/s41467-021-26361-1

Mer information

Senast uppdaterat

2021-11-08