Recent Advances in Metabolic Engineering of Yarrowia lipolytica for Lipid Overproduction

Abstract

The non‐conventional yeast Yarrowia lipolytica have been receiving growing attention due to its excellent lipid accumulation capacity. Microbial lipid have attracted widespread interest due to their broad applications as dietary supplements, cosmetic additives, oleochemicals, and renewable starting materials for the production of fossil fuel. With the development of whole‐genome sequencing, many effective genetic tools, including transformation systems, promoter systems, genomic integration and genome editing tools, have been applied in Y. lipolytica to enhance the overproduction of lipid. It can be genetically engineered for high lipid production via the upregulation of synthetic precursor and lipid synthesis pathways, the downregulation or disruption of competing pathways such as β‐oxidation, and elimination of inhibitory factors. In this review, the lipid metabolism, available genetic tools, and recent advances in metabolic engineering of Y. lipolytica for the overproduction of lipid and lipid‐derived chemicals is summarized. Future prospects of lipid biosynthesis in Y. lipolytica are discussed in light of the current progress, challenges, and trends in this field. Guidelines for future studies are also proposed. Practical Applications: General concerns about climate change, oil price crisis, and the increasing study for renewable energy are driving bio‐lipid as promising alternatives to fossil fuel. Over the past few decades, microbial lipid have been widely applied in dietary supplements, cosmetic additives, oleochemicals, and renewable starting materials for the production of fossil fuel. The non‐conventional yeast Yarrowia lipolytica have become an attractive metabolic engineering host for the production of microbial lipids due to its ability to synthesize them in large quantities. This review illuminates the lipid biosynthesis and degradation of Y. lipolytica, and summarizes the metabolic engineering efforts which have targeted a variety of biosynthetic biosynthetic pathway to efficiently convert carbon source to lipid in oleaginous Y. lipolytica. Schematic diagram of lipid and triacylglyceride biosynthesis, including the native and heterologous biosynthesis pathways of fatty acids in Y. lipolytica.

Iterative cycle of widely targeted metabolic profiling for the improvement of 1-butanol titer and productivity in Synechococcus elongatus

“…However, several reports in Yarrowia lipolytica ( Y. lipolytica) demonstrated the successful overexpression of a single subunit of ACCase for improvement of fuel-like molecules and oleochemicals production [ 29 – 32 ]. Moreover, several studies on the overexpression of ACCase in various microorganisms, such as Escherichia coli [ 33 ] and Saccharomyces cerevisiae [ 34 ] for production of valuable compounds, have also been published.…”

Sustainable Animal Feed Protein through the Cultivation of YARROWIA Lipolytica on Agro-Industrial Wastes and by-Products

“…Given that economic viability of biotechnological processes is significantly affected by the substrate cost, many studies demonstrate the growth of Yarrowia lipolytica on various low-or no-cost substrates, either through the exploitation of the native ability of the yeast to use different carbon sources [19], or after the biotechnological engineering of specific strains to expand the range of fermentable substrates [35]. Numerous reviews [13,22,[43][44][45][46], report the use of various AWCBs as substrate including: olive oil mill wastewater, palm oil mill effluent, soybean oil refinery waste, fishmeal waste, tallow, crude glycerol, lignocellulosic hydrolysates, molasses, waste oils, etc.…”

“…Most reviews focus on the recent advancements concerning the cellular and metabolic engineering of the microorganism either to produce non-native high-value products [17,20,[28][29][30][31][32] or to increase/improve the productivity and yield of conventional products (e.g., citric acid, bio-lipids etc.) [13,19,[33][34][35][36][37][38]. Comparatively, there are fewer reviews describing biotechnological applications of Yarrowia lipolytica growing on alternative low-cost substrates that decrease its cultivation cost; the most recent reviews are provided by Carsaba et al [13] and Spangnuolo et al [22] that summarize relevant studies published till 2017.…”

Characterization of threeYarrowia lipolyticastrains in respect to different cultivation temperatures and metabolite secretion

“…As nitrogen is missing for protein and nucleic acid synthesis cell proliferation stops and the carbon is directed to synthesis of triacylglycerols which are stored in specialised compartments, the lipid bodies. Lipid production with different Y. lipolytica strains, its regulation and optimization is described in numerous publications (Bruder et al 2018a ;Lazar, Liu and Stephanopoulos 2018 ;Zeng et al 2018) .…”