Engineering yeast phospholipid metabolism for de novo oleoylethanolamide production
Journal article, 2019

Phospholipids, the most abundant membrane lipid components, are crucial in maintaining membrane structures and homeostasis for biofunctions. As a structurally diverse and tightly regulated system involved in multiple organelles, phospholipid metabolism is complicated to manipulate. Thus, repurposing phospholipids for lipid-derived chemical production remains unexplored. Herein, we develop a Saccharomyces cerevisiae platform for de novo production of oleoylethanolamide, a phospholipid derivative with promising pharmacological applications in ameliorating lipid dysfunction and neurobehavioral symptoms. Through deregulation of phospholipid metabolism, screening of biosynthetic enzymes, engineering of subcellular trafficking and process optimization, we could produce oleoylethanolamide at a titer of 8,115.7 µg l−1 and a yield on glucose of 405.8 µg g−1. Our work provides a proof-of-concept study for systemically repurposing phospholipid metabolism for conversion towards value-added biological chemicals, and this multi-faceted framework may shed light on tailoring phospholipid metabolism in other microbial hosts.

Author

Yi Liu

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Quanli Liu

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Anastasia Krivoruchko

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Sakda Khoomrung

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Mahidol University

Jens B Nielsen

Technical University of Denmark (DTU)

BioInnovation Institute

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Nature Chemical Biology

1552-4450 (ISSN) 1552-4469 (eISSN)

Vol. In Press

Biological Production Systems 2014

Swedish Foundation for Strategic Research (SSF), 2015-01-01 -- 2020-12-31.

Swedish Foundation for Strategic Research (SSF), 2015-01-01 -- 2020-12-31.

Subject Categories

Production Engineering, Human Work Science and Ergonomics

Embedded Systems

Biocatalysis and Enzyme Technology

DOI

10.1038/s41589-019-0431-2

More information

Latest update

1/9/2020 3