De novo biosynthesis of rubusoside and rebaudiosides in engineered yeasts

Yameng Xu, Xinglong Wang, Chenyang Zhang, Xuan Zhou, Xianhao Xu, Luyao Han, Xueqin Lv, Yanfeng Liu, Song Liu, Jianghua Li, Guocheng Du, Jian Chen, Rodrigo Ledesma-Amaro and Long Liu ()
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Yameng Xu: Jiangnan University
Xinglong Wang: Jiangnan University
Chenyang Zhang: Jiangnan University
Xuan Zhou: Jiangnan University
Xianhao Xu: Jiangnan University
Luyao Han: Jiangnan University
Xueqin Lv: Jiangnan University
Yanfeng Liu: Jiangnan University
Song Liu: Jiangnan University
Jianghua Li: Jiangnan University
Guocheng Du: Jiangnan University
Jian Chen: Jiangnan University
Rodrigo Ledesma-Amaro: Imperial College London
Long Liu: Jiangnan University

Nature Communications, 2022, vol. 13, issue 1, 1-12

Abstract: Abstract High-sugar diet causes health problems, many of which can be addressed with the use of sugar substitutes. Rubusoside and rebaudiosides are interesting molecules, considered the next generation of sugar substitutes due to their low-calorie, superior sweetness and organoleptic properties. However, their low abundance in nature makes the traditional plant extraction process neither economical nor environmental-friendly. Here we engineer baker’s yeast Saccharomyces cerevisiae as a chassis for the de novo production of rubusoside and rebaudiosides. In this process, we identify multiple issues that limit the production, including rate-liming steps, product stress on cellular fitness and unbalanced metabolic networks. We carry out a systematic engineering strategy to solve these issues, which produces rubusoside and rebaudiosides at titers of 1368.6 mg/L and 132.7 mg/L, respectively. The rubusoside chassis strain here constructed paves the way towards a sustainable, large-scale fermentation-based manufacturing of diverse rebaudiosides.

Date: 2022
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30826-2

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DOI: 10.1038/s41467-022-30826-2

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