title: Metabolic engineering of microorganisms to produce omega-3 very long-chain polyunsaturated fatty acids.
abstract: Omega-3 long-chain polyunsaturated fatty acids (LC-PUFAs) have received growing attention due to their significant roles in human health. Currently the main source of these nutritionally and medically important fatty acids is marine fish, which has not met ever-increasing global demand. Microorganisms are an important alternative source also being explored. Although many microorganisms accumulate omega-3 LC-PUFAs naturally, metabolic engineering might still be necessary for significantly improving their yields. Here, we review recent research involving the engineering of microorganisms for production of omega-3 LC-PUFAs, including eicospentaenoic acid and docosohexaenoic acid. Both reconstitution of omega-3 LC-PUFA biosynthetic pathways and modification of existing pathways in microorganisms have demonstrated the potential to produce high levels of omega-3 LC-PUFAs. However, the yields of omega-3 LC-PUFAs in host systems have been substantially limited by potential metabolic bottlenecks, which might be caused partly by inefficient flux of fatty acid intermediates between the acyl-CoA and different lipid class pools. Although fatty acid flux in both native and heterologous microbial hosts might be controlled by several acyltransferases, evidence has suggested that genetic manipulation of one acyltransferase alone could significantly increase the accumulation of LC-PUFAs. The number of oleaginous microorganisms that can be genetically transformed is increasing, which will advance engineering efforts to maximize LC-PUFA yields in microbial strains.
authors.affiliation: Key Laboratory of Biology and Genetic Improvement of Oil Crops, Ministry of Agriculture, Oil Crops Research Institute of Chinese Academy of Agricultural Sciences, No. 2 Xudong Second Road, Wuhan 430062, PR China. Electronic address: gongyangmin@caas.cn.
authors.forename: Yangmin
authors.initials: Y
authors.lastname: Gong
authors.affiliation: Key Laboratory of Biology and Genetic Improvement of Oil Crops, Ministry of Agriculture, Oil Crops Research Institute of Chinese Academy of Agricultural Sciences, No. 2 Xudong Second Road, Wuhan 430062, PR China.
authors.forename: Xia
authors.initials: X
authors.lastname: Wan
authors.affiliation: Key Laboratory of Biology and Genetic Improvement of Oil Crops, Ministry of Agriculture, Oil Crops Research Institute of Chinese Academy of Agricultural Sciences, No. 2 Xudong Second Road, Wuhan 430062, PR China.
authors.forename: Mulan
authors.initials: M
authors.lastname: Jiang
authors.affiliation: Key Laboratory of Biology and Genetic Improvement of Oil Crops, Ministry of Agriculture, Oil Crops Research Institute of Chinese Academy of Agricultural Sciences, No. 2 Xudong Second Road, Wuhan 430062, PR China.
authors.forename: Chuanjiong
authors.initials: C
authors.lastname: Hu
authors.affiliation: Key Laboratory of Algal Biology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, PR China.
authors.forename: Hanhua
authors.initials: H
authors.lastname: Hu
authors.affiliation: Hubei Key Laboratory of Lipid Chemistry and Nutrition, Oil Crops Research Institute of Chinese Academy of Agricultural Sciences, No. 2 Xudong Second Road, Wuhan 430062, PR China.
authors.forename: Fenghong
authors.initials: F
authors.lastname: Huang
mesh_terms: D001419:Bacteria / Q000235:genetics* / Q000378:metabolism; D053898:Biosynthetic Pathways / Q000235:genetics*; D015525:Fatty Acids, Omega-3 / Q000096:biosynthesis*; D005658:Fungi / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007218:Industrial Microbiology / Q000379:methods; D060847:Metabolic Engineering / Q000379:methods*; D058086:Microalgae / Q000235:genetics* / Q000378:metabolism; D015203:Reproducibility of Results
chemical_list: D015525:Fatty Acids, Omega-3
keywords: Desaturases; Elongases; Metabolic engineering; Microorganisms; Omega-3 fatty acids; Polyketide synthase-like pathway