De Novo Biosynthesis of Rubusoside and Rebaudiosides in Engineered Yeasts

Overview

Journal Nat Commun

Specialty Biology

Date 2022 Jun 1

PMID 35650215

Authors

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

Long Liu

Affiliations

Soon will be listed here.

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.

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