Multidimensional engineering of Saccharomyces cerevisiae for efficient synthesis of medium-chain fatty acids
Artikel i vetenskaplig tidskrift, 2020

Medium-chain fatty acids (MCFAs; C6–C12) are valuable molecules used for biofuel and oleochemical production; however, it is challenging to synthesize these fatty acids efficiently using microbial biocatalysts due to the cellular toxicity of MCFAs. In this study, both the endogenous fatty acid synthase (FAS) and an orthogonal bacterial type I FAS were engineered for MCFA production in the yeast Saccharomyces cerevisiae. To improve cellular tolerance to toxic MCFAs, we performed directed evolution of the membrane transporter Tpo1 and strain adaptive laboratory evolution, which elevated the MCFA production by 1.3 ± 0.3- and 1.7 ± 0.2-fold, respectively. We therefore further engineered the highly resistant strain to augment the metabolic flux towards MCFAs. This multidimensional engineering of the yeast at the single protein/enzyme level, the pathway level and the cellular level, combined with an optimized cultivation process, resulted in the production of >1 g l−1 extracellular MCFAs—a more than 250-fold improvement over the original strain.

Författare

Zhu Zhiwei

Dalian University of Technology

Chalmers, Biologi och bioteknik, Systembiologi

Yating Hu

Chalmers, Biologi och bioteknik, Systembiologi

Paulo Teixeira

Chalmers, Biologi och bioteknik, Systembiologi

Rui Pereira

Chalmers, Biologi och bioteknik, Systembiologi

Yun Chen

Novo Nordisk Foundation Center for Biosustainability

Chalmers, Biologi och bioteknik, Systembiologi

Verena Siewers

Chalmers, Biologi och bioteknik, Systembiologi

Jens B Nielsen

BioInnovation Institute

Danmarks Tekniske Universitet (DTU)

Chalmers, Biologi och bioteknik, Systembiologi

Nature Catalysis

25201158 (eISSN)

Vol. 3 1 64-74

Ämneskategorier

Biokemi och molekylärbiologi

Mikrobiologi

Biokatalys och enzymteknik

DOI

10.1038/s41929-019-0409-1

Mer information

Senast uppdaterat

2020-02-28