Engineering yeast phospholipid metabolism for de novo oleoylethanolamide production
Artikel i vetenskaplig tidskrift, 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.

Författare

Yi Liu

Chalmers, Biologi och bioteknik, Systembiologi

Quanli Liu

Chalmers, Biologi och bioteknik, Systembiologi

Anastasia Krivoruchko

Chalmers, Biologi och bioteknik, Systembiologi

Sakda Khoomrung

Chalmers, Biologi och bioteknik, Systembiologi

Mahidol University

Jens B Nielsen

Danmarks Tekniske Universitet (DTU)

BioInnovation Institute

Chalmers, Biologi och bioteknik, Systembiologi

Nature Chemical Biology

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

Vol. In Press

Bioteknisk produktion av värdeskapande ingredienser

Stiftelsen för Strategisk forskning (SSF), 2015-01-01 -- 2020-12-31.

Stiftelsen för Strategisk forskning (SSF), 2015-01-01 -- 2020-12-31.

Ämneskategorier

Produktionsteknik, arbetsvetenskap och ergonomi

Inbäddad systemteknik

Biokatalys och enzymteknik

DOI

10.1038/s41589-019-0431-2

Mer information

Senast uppdaterat

2020-01-09