Lipid engineering combined with systematic metabolic engineering of Saccharomyces cerevisiae for high-yield production of lycopene
Journal article, 2019

Saccharomyces cerevisiae is an efficient host for natural-compound production and preferentially employed in academic studies and bioindustries. However, S. cerevisiae exhibits limited production capacity for lipophilic natural products, especially compounds that accumulate intracellularly, such as polyketides and carotenoids, with some engineered compounds displaying cytotoxicity. In this study, we used a nature-inspired strategy to establish an effective platform to improve lipid oil–triacylglycerol (TAG) metabolism and enable increased lycopene accumulation. Through systematic traditional engineering methods, we achieved relatively high-level production at 56.2 mg lycopene/g cell dry weight (cdw). To focus on TAG metabolism in order to increase lycopene accumulation, we overexpressed key genes associated with fatty acid synthesis and TAG production, followed by modulation of TAG fatty acyl composition by overexpressing a fatty acid desaturase (OLE1) and deletion of Seipin (FLD1), which regulates lipid-droplet size. Results showed that the engineered strain produced 70.5 mg lycopene/g cdw, a 25% increase relative to the original high-yield strain, with lycopene production reaching 2.37 g/L and 73.3 mg/g cdw in fed-batch fermentation and representing the highest lycopene yield in S. cerevisiae reported to date. These findings offer an effective strategy for extended systematic metabolic engineering through lipid engineering.

Systematic metabolic engineering

Lycopene

Triacylglycerol

Saccharomyces cerevisiae

Lipid engineering

Author

Tian Ma

Wuhan University

Bin Shi

Wuhan University

Ziling Ye

J1 Biotech Co., Ltd.

Xiaowei Li

Wuhan University

Min Liu

Wuhan University

Yun Chen

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Jiang Xia

Chinese University of Hong Kong

Jens Christian Froslev Nielsen

Novo Nordisk Foundation Center for Biosustainability

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Technical University of Denmark (DTU)

Zixin Deng

Wuhan University

Shanghai Jiao Tong University

Tiangang Liu

Wuhan University

Wuhan University of Technology

Metabolic Engineering

1096-7176 (ISSN) 1096-7184 (eISSN)

Vol. 52 134-142

Subject Categories

Microbiology

Biocatalysis and Enzyme Technology

Other Industrial Biotechnology

DOI

10.1016/j.ymben.2018.11.009

More information

Latest update

4/8/2019 1