Biotechnology Bulletin ›› 2024, Vol. 40 ›› Issue (1): 72-85.doi: 10.13560/j.cnki.biotech.bull.1985.2023-0657
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HE Si-cheng(), ZHANG Zi-yuan, HAN Yu-qing, MIAO Lin, ZHANG Cui-ying, YU Ai-qun()
Received:
2023-07-11
Online:
2024-01-26
Published:
2024-02-06
Contact:
YU Ai-qun
E-mail:hesicheng2002@tust.edu.cn;yuaiqun@tust.edu.cn
HE Si-cheng, ZHANG Zi-yuan, HAN Yu-qing, MIAO Lin, ZHANG Cui-ying, YU Ai-qun. Research Progress in the Production of Polyunsaturated Fatty Acids by Yarrowia lipolytica Cell Factories[J]. Biotechnology Bulletin, 2024, 40(1): 72-85.
名称Name | 学名Scientific name | 简称Abbreviation | 功能Functions |
---|---|---|---|
ω-3 PUFA | |||
α-亚麻酸(α-linolenic acid, ALA) | ∆9, ∆12, ∆15-十八碳三烯酸 | Cl8:3n-3或ω-3 18:3 | 抗血栓、降血脂、预防心肌梗塞、维持视网膜等神经系统所必需的营养因子等 |
二十碳五烯酸(Eicosapentaenoic acid, EPA) | ∆5, ∆8, ∆11, ∆14, ∆17-二十碳五烯酸 | C20:5n-3或ω-3 20:5 | 降低心血管疾病的发病率、改善免疫细胞功能、预防及治疗糖尿病等代谢类疾病、预防阿尔兹海默症等 |
二十二碳五烯酸(Docosapentaenoic acid, DPA) | ∆7, ∆10, ∆13, ∆16, ∆19-二十二碳五烯酸 | C22:5n-3或ω-3 22:5 | 抑制炎症、抑制血小板凝聚、对颈动脉粥样硬化具有保护作用、抑制神经炎症等 |
二十二碳六烯酸(Docosahexaenoic acid, DHA) | ∆4, ∆7, ∆10, ∆13, ∆16, ∆19-二十二碳六烯酸 | C22:6n-3或ω-3 22:6 | 促进脑细胞及神经系统发育、预防心脑血管疾病,调节中枢神经功能等 |
ω-6 PUFA | |||
亚油酸(Linolenic acid, LA) | ∆9, ∆12-十八碳二烯酸 | Cl8:2n-6或ω-6 18:2 | 预防代谢疾病和癌症、抗动脉粥样硬化、抑制肥胖、调节免疫系统等 |
γ-亚麻酸(γ-linolenic acid, GLA) | ∆6, ∆9, ∆12-十八碳三烯酸 | Cl8:3n-6或ω-6 18:3 | 抗炎症、抗心血管疾病、抗肿瘤、抗糖尿病、缓解更年期综合征等 |
二高-γ-亚麻酸(Dohomo-γ-linolenic acid, DGLA) | ∆6, ∆9, ∆12-二十碳三烯酸 | C20:3n-6或ω-6 20:3 | 抑制血栓素活性、抑制血小板凝聚及细胞分裂素分泌、抗动脉粥样硬化等 |
花生四烯酸(Arachidonic acid, ARA) | ∆5, ∆8, ∆11, ∆14-二十碳四烯酸 | C20:4n-6或ω-6 20:4 | 合成人体前列腺素的重要前体物质、促进婴幼儿大脑发育、抑制人体各类型皮肤疾病病理发展等 |
Table 1 The most common types of PUFA in organisms
名称Name | 学名Scientific name | 简称Abbreviation | 功能Functions |
---|---|---|---|
ω-3 PUFA | |||
α-亚麻酸(α-linolenic acid, ALA) | ∆9, ∆12, ∆15-十八碳三烯酸 | Cl8:3n-3或ω-3 18:3 | 抗血栓、降血脂、预防心肌梗塞、维持视网膜等神经系统所必需的营养因子等 |
二十碳五烯酸(Eicosapentaenoic acid, EPA) | ∆5, ∆8, ∆11, ∆14, ∆17-二十碳五烯酸 | C20:5n-3或ω-3 20:5 | 降低心血管疾病的发病率、改善免疫细胞功能、预防及治疗糖尿病等代谢类疾病、预防阿尔兹海默症等 |
二十二碳五烯酸(Docosapentaenoic acid, DPA) | ∆7, ∆10, ∆13, ∆16, ∆19-二十二碳五烯酸 | C22:5n-3或ω-3 22:5 | 抑制炎症、抑制血小板凝聚、对颈动脉粥样硬化具有保护作用、抑制神经炎症等 |
二十二碳六烯酸(Docosahexaenoic acid, DHA) | ∆4, ∆7, ∆10, ∆13, ∆16, ∆19-二十二碳六烯酸 | C22:6n-3或ω-3 22:6 | 促进脑细胞及神经系统发育、预防心脑血管疾病,调节中枢神经功能等 |
ω-6 PUFA | |||
亚油酸(Linolenic acid, LA) | ∆9, ∆12-十八碳二烯酸 | Cl8:2n-6或ω-6 18:2 | 预防代谢疾病和癌症、抗动脉粥样硬化、抑制肥胖、调节免疫系统等 |
γ-亚麻酸(γ-linolenic acid, GLA) | ∆6, ∆9, ∆12-十八碳三烯酸 | Cl8:3n-6或ω-6 18:3 | 抗炎症、抗心血管疾病、抗肿瘤、抗糖尿病、缓解更年期综合征等 |
二高-γ-亚麻酸(Dohomo-γ-linolenic acid, DGLA) | ∆6, ∆9, ∆12-二十碳三烯酸 | C20:3n-6或ω-6 20:3 | 抑制血栓素活性、抑制血小板凝聚及细胞分裂素分泌、抗动脉粥样硬化等 |
花生四烯酸(Arachidonic acid, ARA) | ∆5, ∆8, ∆11, ∆14-二十碳四烯酸 | C20:4n-6或ω-6 20:4 | 合成人体前列腺素的重要前体物质、促进婴幼儿大脑发育、抑制人体各类型皮肤疾病病理发展等 |
Fig. 1 Schematic diagram of the PUFA synthetic pathway in Y. lipolytica In this figure, the solid line indicates the native fatty acid synthesis pathway in Y. lipolytica cells, and the dotted line indicates the heterologous PUFA pathway constructed in Y. lipolytica through metabolic engineering
类型Type | 名称Names | 特征Characteristics | 参考文献Reference |
---|---|---|---|
组成型启动子 Constitutive promoters | pTEF | 内源 | [ |
pTDH1、pGPM1、pFBAIN | 内源 | [ | |
pEXP1、pGPAT、pGPD | 内源 | [ | |
pDGA1、pACC、pIDH2、pFAS2、pFAS1、pPOX4、pZWF1、pIDP2 | 内源 | [ | |
pTEFin | 内源 | [ | |
诱导型启动子 Inducible promoters | pGAP、pACL2 | 内源 | [ |
pXPR2 | 内源;肽诱导型 | [ | |
pPOX2、pPOT1 | 内源;脂肪酸、烷烃及蓖麻油酸甲酯诱导型;葡萄糖及甘油阻遏型 | [ | |
pLIP2、pALK1 | 内源;脂肪酸及烷烃诱导型 | [ | |
pYAT1 | 内源;低氮诱导型 | [ | |
pEYK1、pEYD1 | 内源;赤藓醇及赤藓糖诱导型;葡萄糖及甘油阻遏型 | [ | |
pALK1 | 内源;正癸烷诱导型;甘油阻遏型 | [ | |
pPAT1 | 内源;正癸烷及油酸诱导型;甘油阻遏型 | [ | |
pTHR1、pMET3、pSER1、pCTR1、pCTR2 | 内源;铜阻遏型 | [ | |
pHP4d | 杂合 | [ | |
pnUAS1XPR2-LEU、pnUAS1XPR2-TEF | 杂合 | [ | |
pEYK1-nAB、pEYK1-4AB-coreTEF, pEYK1/EYD1B-coreEYK1 | 杂合;赤藓醇及赤藓糖诱导型;葡萄糖及甘油阻遏型 | [ | |
pTEFR1 | 杂合;脂肪酰基辅酶A诱导型 | [ | |
p(A1R1)×2A3 | 杂合;油酸诱导型 | [ |
Table 2 Most prominently used promoters for heterologous expression in Y. lipolytica
类型Type | 名称Names | 特征Characteristics | 参考文献Reference |
---|---|---|---|
组成型启动子 Constitutive promoters | pTEF | 内源 | [ |
pTDH1、pGPM1、pFBAIN | 内源 | [ | |
pEXP1、pGPAT、pGPD | 内源 | [ | |
pDGA1、pACC、pIDH2、pFAS2、pFAS1、pPOX4、pZWF1、pIDP2 | 内源 | [ | |
pTEFin | 内源 | [ | |
诱导型启动子 Inducible promoters | pGAP、pACL2 | 内源 | [ |
pXPR2 | 内源;肽诱导型 | [ | |
pPOX2、pPOT1 | 内源;脂肪酸、烷烃及蓖麻油酸甲酯诱导型;葡萄糖及甘油阻遏型 | [ | |
pLIP2、pALK1 | 内源;脂肪酸及烷烃诱导型 | [ | |
pYAT1 | 内源;低氮诱导型 | [ | |
pEYK1、pEYD1 | 内源;赤藓醇及赤藓糖诱导型;葡萄糖及甘油阻遏型 | [ | |
pALK1 | 内源;正癸烷诱导型;甘油阻遏型 | [ | |
pPAT1 | 内源;正癸烷及油酸诱导型;甘油阻遏型 | [ | |
pTHR1、pMET3、pSER1、pCTR1、pCTR2 | 内源;铜阻遏型 | [ | |
pHP4d | 杂合 | [ | |
pnUAS1XPR2-LEU、pnUAS1XPR2-TEF | 杂合 | [ | |
pEYK1-nAB、pEYK1-4AB-coreTEF, pEYK1/EYD1B-coreEYK1 | 杂合;赤藓醇及赤藓糖诱导型;葡萄糖及甘油阻遏型 | [ | |
pTEFR1 | 杂合;脂肪酰基辅酶A诱导型 | [ | |
p(A1R1)×2A3 | 杂合;油酸诱导型 | [ |
工程菌株 Engineered strain | 多不饱和脂肪酸 PUFA | 最高产量 Maximum titer | 占总脂肪酸含量Proportion of TFA/% | 参考文献References |
---|---|---|---|---|
小球藻(Chlorella vulgaris) | ALA | — | 10.8 | [ |
圆红冬孢酵母(R. kratochvilovae) | ALA | — | 5.9 | [ |
解脂耶氏酵母(Y. lipolytica) | ALA | 1 400 mg/L | 28 | [ |
裂殖壶菌(Schizochytrium sp.) | EPA | 1 740 mg/L | 1.9 | [ |
大肠杆菌(Escherichia coli) | EPA | 31.4 mg/g DCW | — | [ |
解脂耶氏酵母(Y. lipolytica) | EPA | 3 200 mg/L | 56.6 | [ |
酿酒酵母(S. cerevisiae) | DHA | 39.6 mg/L | 10.2 | [ |
恶臭假单孢菌(Paseudomonas putida) | DHA | 1.4 mg/g | — | [ |
解脂耶氏酵母(Y. lipolytica) | DHA | 86.5 mg/L(12.8 mg/g DCW) | 10.5 | [ |
解脂耶氏酵母(Y. lipolytica) | CLA | 4 000 mg/L | 44 | [ |
解脂耶氏酵母(Y. lipolytica) | ARA | 118.1 mg/L | — | [ |
Table 3 Representative examples of PUFA production by metabolically engineered microorganisms
工程菌株 Engineered strain | 多不饱和脂肪酸 PUFA | 最高产量 Maximum titer | 占总脂肪酸含量Proportion of TFA/% | 参考文献References |
---|---|---|---|---|
小球藻(Chlorella vulgaris) | ALA | — | 10.8 | [ |
圆红冬孢酵母(R. kratochvilovae) | ALA | — | 5.9 | [ |
解脂耶氏酵母(Y. lipolytica) | ALA | 1 400 mg/L | 28 | [ |
裂殖壶菌(Schizochytrium sp.) | EPA | 1 740 mg/L | 1.9 | [ |
大肠杆菌(Escherichia coli) | EPA | 31.4 mg/g DCW | — | [ |
解脂耶氏酵母(Y. lipolytica) | EPA | 3 200 mg/L | 56.6 | [ |
酿酒酵母(S. cerevisiae) | DHA | 39.6 mg/L | 10.2 | [ |
恶臭假单孢菌(Paseudomonas putida) | DHA | 1.4 mg/g | — | [ |
解脂耶氏酵母(Y. lipolytica) | DHA | 86.5 mg/L(12.8 mg/g DCW) | 10.5 | [ |
解脂耶氏酵母(Y. lipolytica) | CLA | 4 000 mg/L | 44 | [ |
解脂耶氏酵母(Y. lipolytica) | ARA | 118.1 mg/L | — | [ |
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