Synthetic biology, systems biology, and metabolic engineering of Yarrowia lipolytica toward a sustainable biorefinery platform

Abstract

Yarrowia lipolytica is an oleaginous yeast that has been substantially engineered for production of oleochemicals and drop-in transportation fuels. The unique acetyl-CoA/malonyl-CoA supply mode along with the versatile carbon-utilization pathways makes this yeast a superior host to upgrade low-value carbons into high-value secondary metabolites and fatty acid-based chemicals. The expanded synthetic biology toolkits enabled us to explore a large portfolio of specialized metabolism beyond fatty acids and lipid-based chemicals. In this review, we will summarize the recent advances in genetic, omics, and computational tool development that enables us to streamline the genetic or genomic modification for Y. lipolytica. We will also summarize various metabolic engineering strategies to harness the endogenous acetyl-CoA/malonyl-CoA/HMG-CoA pathway for production of complex oleochemicals, polyols, terpenes, polyketides, and commodity chemicals. We envision that Y. lipolytica will be an excellent microbial chassis to expand nature’s biosynthetic capacity to produce plant secondary metabolites, industrially relevant oleochemicals, agrochemicals, commodity, and specialty chemicals and empower us to build a sustainable biorefinery platform that contributes to the prosperity of a bio-based economy in the future.

Genetic and bioprocess engineering to improve squalene production in Yarrowia lipolytica

“…Yarrowia lipolytica is an industrial oleaginous yeast that has been extensively engineered to synthesize lipophilic compounds, including lipids ( Qiao et al, 2017 ), oleochemicals ( Xu et al, 2016 ), carotenoids ( Larroude et al, 2018 ), terpenoids ( Jin et al, 2019 ) and aromatic polyketides ( Czajka et al, 2018 , Lv et al, 2019b ) et al The lipogeneity of this yeast makes it a superior host to produce chemicals that are derived from acetyl-CoA, malonyl-CoA, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) and NADPHs ( Gu et al, 2020 , Ma et al, 2020 ). The compartmentalization of oil droplets into lipid bodies provides a hydrophobic environment to sequester many lipid-related compounds and mitigate the toxicity issues associated with lipophilic membrane damages.…”

Yeast-Based Biosynthesis of Natural Products From Xylose

“…and artificial genomes (Guo et al, 2020) has greatly facilitated genetic modifications, although delicate design is always required. A detailed description of all the genetic tools and strategies suitable for Y. lipolytica engineering can be found in a very recent review (Ma et al, 2020).…”

Yarrowia lipolytica as an Oleaginous Platform for the Production of Value-Added Fatty Acid-Based Bioproducts

“…In particular, the different metabolic engineering strategies are applied in the lipid production for Y. lipolytica (Abdel-Mawgoud et al, 2018;. In fact, Y. lipolytica is able to produce fatty acids in the form of lipids, either grown on hydrophilic or hydrophobic materials (Spagnuolo et al, 2018;Ma et al, 2020). Generally, these fatty acid-based bioproducts from Y. lipolytica are divided into three different types, based on the chain length, the terminal…”