Synthetic biology, systems biology, and metabolic engineering of Yarrowia lipolytica toward a sustainable biorefinery pl
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METABOLIC ENGINEERING AND SYNTHETIC BIOLOGY - REVIEW
Synthetic biology, systems biology, and metabolic engineering of Yarrowia lipolytica toward a sustainable biorefinery platform Jingbo Ma1 · Yang Gu1 · Monireh Marsafari1,2 · Peng Xu1 Received: 25 March 2020 / Accepted: 25 June 2020 © Society for Industrial Microbiology and Biotechnology 2020
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 acidbased 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. Keywords Yarrowia lipolytica · Synthetic biology · Systems biology · Metabolic engineering · Biofuel · Natural products · Chemicals
Introduction With the rapid development of metabolic engineering and synthetic biology, a variety of economic and green chemicals have been produced from microbes at low cost from renewable feedstocks [1]. Oleaginous yeasts have emerged as the unique industrial workhorse for lipid-derived bioproduction owing to their exceptional abilities in accumulating intracellular lipids and utilizing cost-efficient substrates [2]. Yarrowia lipolytica, the non-conventional oleaginous organism, has been well studied and applied for industrial bioproduction due to its metabolic plasticity and generally regarded as safe (GRAS) status [3, 4]. Y. lipolytica natively has high tricarboxylic acid (TCA) cycle and acetyl-CoA fluxes, and * Peng Xu [email protected] 1
Department of Chemical, Biochemical and Environmental Engineering, University of Maryland, Baltimore County, Baltimore, MD 21250, USA
Department of Agronomy and Plant Breeding, University of Guilan, Rasht, Islamic Republic of Iran
2
high levels of free fatty acids (FAs) and triacylglycerols (TAGs); it has been engineered for the production of organic acids, acetyl-CoA derivatives, fatty acid (FA)-derived, and lipid-based products [5, 6]. In addition, Y. lipolytica can utilize and grow on var
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