2-苯乙醇生物合成的研究进展

doi:10.12211/2096-8280.2020-096

合成生物学 ›› 2021, Vol. 2 ›› Issue (6): 1030-1045.DOI: 10.12211/2096-8280.2020-096

2-苯乙醇生物合成的研究进展

严伟¹, 高豪¹, 蒋羽佳¹, 钱秀娟¹, 周杰^1,², 董维亮^1,², 章文明^1,², 信丰学^1,², 姜岷^1,²

^1.南京工业大学生物与制药工程学院，材料化学工程国家重点实验室，江苏南京 211816
^2.南京工业大学江苏先进生物与化学制造协同创新中心（SICAM），江苏南京 211816

收稿日期:2020-12-31 修回日期:2021-03-10 出版日期:2021-12-31 发布日期:2022-01-21
通讯作者: 信丰学,姜岷
作者简介:严伟（1993—），男，博士。研究方向为代谢工程及合成生物学。E-mail：15051801815@163.com|信丰学（1982—），男，博士，教授。研究方向为生物化工与生物能源。E-mail：xinfengxue@njtech.edu.cn|姜岷（1972—），男，博士，教授。研究方向为生物转化与生物催化。E-mail：jiangmin@njtech.edu.cn
基金资助:
国家重点研发计划“合成生物学”重点专项(2018YFA0902200);国家自然科学基金(22178169);江苏省自然科学基金(BK20200683)

Research progress in 2-phenylethanol production through biological processes

Wei YAN¹, Hao GAO¹, Yujia JIANG¹, Xiujuan QIAN¹, Jie ZHOU^1,², Weiliang DONG^1,², Wenming ZHANG^1,², Fengxue XIN^1,², Min JIANG^1,²

^1.State Key Laboratory of Materials-Oriented Chemical Engineering，College of Biotechnology and Pharmaceutical Engineering，Nanjing Tech University，Nanjing 211816，Jiangsu，China
^2.Jiangsu National Synergetic Innovation Center for Advanced Materials （SICAM），Nanjing Tech University，Nanjing 211816，Jiangsu，China

Received:2020-12-31 Revised:2021-03-10 Online:2021-12-31 Published:2022-01-21
Contact: Fengxue XIN,Min JIANG

摘要/Abstract

摘要：

2-苯乙醇（2-PE）是一种具有玫瑰香味的重要香料化合物，广泛应用于化妆品、香水、食品等行业。传统的2-PE生产主要是从植物原料中提取或化学合成。然而，这些方法无法满足消费者对天然香料日益增长的需求。以发酵法或酶法生产的L-苯丙氨酸为前体，利用酵母细胞将其转化为2-PE，产品既符合环境友好的要求，又满足“天然”产品的定义，可以取代从玫瑰或其他植物精油中提取的天然2-PE。因此，生物法合成2-PE已经引起人们的广泛关注。本文综述了生物法合成2-PE的现状和发展前景，指出相对于传统的化学合成和天然植物提取，生物转化比较具有优越性。并对2-PE的合成途径、全局调控机制、提高2-PE产量的策略以及农工废弃物作为原料的利用进行了系统的论述。此外，本文还讨论了原位产物分离技术在2-PE生物合成中的应用。

关键词: 2-苯乙醇, 生物合成, 全局调控, 代谢工程, 原位萃取

Abstract:

2-Phenylethanol (2-PE), an important flavor and fragrance compound with a rose-like smell has been widely used in the cosmetics, perfume, and food industries. Furthermore, it is also an important raw material for the derivatives synthesis for the synthesis of other flavors or pharmaceutical compounds, such as 2-phenylethylacetate (2-PEAc) and phenylacetaldehyde (PA). Conventional production of 2-PE is mainly through the extraction from plant materials, such as hyacinths, jasmine and lilies. However, the extraction process is very complicated and the harvest of flowers is greatly influenced by the weather, plant diseases, and trade restrictions, which hinders its further application. On the other hand, 2-PE can also be chemically synthesized through ethylene oxidation of benzene or reduction of styrene oxide. Chemical synthesis processes are generally operated under harsh conditions, such as high temperature, high pressure, and strong acid or alkali environments, producing many undesirable by-products, such as ethylbenzene and styrene. This not only increases the downstream costs, but also seriously debases the grade of 2-PE. The increasing demand for environmental friendly processes and the preference for “natural” products from consumers have considerably stimulated the development of biological production of flavors and fragrances. Biological synthesis of 2-PE has attracted extensive attention because it meets the requirements of environmental friendliness and also satisfies the definition of “natural” products. However, the toxicity of 2-PE to cells is a critical limiting factor for the biosynthesis of 2-PE. In this review, we have comprehensively summarized the current status and perspectives for biological 2-PE production in terms of its advantages over classical chemical synthesis and extraction from natural plants. A comprehensive description of 2-PE synthetic pathways and global regulation mechanisms, strategies to increase 2-PE production, and the utilization of agro-industrial wastes as feedstocks has been systematically discussed. Furthermore, the application of in situ product removal techniques in 2-PE biosynthesis has also been highlighted.

Key words: 2-phenylethanol, biological production, regulatory network, metabolic engineering, ISPR techniques

中图分类号:

严伟, 高豪, 蒋羽佳, 钱秀娟, 周杰, 董维亮, 章文明, 信丰学, 姜岷. 2-苯乙醇生物合成的研究进展[J]. 合成生物学, 2021, 2(6): 1030-1045.

Wei YAN, Hao GAO, Yujia JIANG, Xiujuan QIAN, Jie ZHOU, Weiliang DONG, Wenming ZHANG, Fengxue XIN, Min JIANG. Research progress in 2-phenylethanol production through biological processes[J]. Synthetic Biology Journal, 2021, 2(6): 1030-1045.

图/表 5

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菌株	方法	条件优化	2-PE产量/（g/L）	发酵体积	参考文献
产甘油假单胞菌WL2002-5	单因素设计	培养基成分、温度	5.0	3 L	[51]
马克思克鲁维酵母CBS600	遗传算法	培养基成分、温度	5.6	50 mL	[11]
酿酒酵母CWY132	单因素设计	培养基成分、接种量	3.52	2 L	[56]
酿酒酵母	单因素、正交设计、Box-Behnken 中心复合设计和响应面方法	培养基成分	4.82	30 mL	[61]
马克思克鲁维酵母	中心复合材料设计与响应面方法	L-苯丙氨酸浓度、pH、温度	0.47	50 mL	[71]
酿酒酵母	Plackett-Burman设计, steepest ascent 设计与Box-Behnken 设计	培养基成分、pH、发酵时间	1.55	50 mL	[72]

菌株	方法	条件优化	2-PE产量/（g/L）	发酵体积	参考文献
产甘油假单胞菌WL2002-5	单因素设计	培养基成分、温度	5.0	3 L	[51]
马克思克鲁维酵母CBS600	遗传算法	培养基成分、温度	5.6	50 mL	[11]
酿酒酵母CWY132	单因素设计	培养基成分、接种量	3.52	2 L	[56]
酿酒酵母	单因素、正交设计、Box-Behnken 中心复合设计和响应面方法	培养基成分	4.82	30 mL	[61]
马克思克鲁维酵母	中心复合材料设计与响应面方法	L-苯丙氨酸浓度、pH、温度	0.47	50 mL	[71]
酿酒酵母	Plackett-Burman设计, steepest ascent 设计与Box-Behnken 设计	培养基成分、pH、发酵时间	1.55	50 mL	[72]

技术	优势	劣势	材料	2-PE产量	参考文献
超临界CO₂萃取	高效萃取力	剧毒，需要先去除细胞	超临界二氧化碳	可以提取90%以上的2-PE	[100]
液-液萃取	低成本，简单，高效，易扩展	有毒性，形成乳状液难以蒸发和去除	聚丙二醇1500	共7.5 g/L，有机相22 g/L	[82]
			聚丙二醇1200	共10.2 g/L，有机相26.5 g/L	[101]
			油酸	共12.6 g/L，有机相24 g/L	[69]
			油醇	共3.0 g/L	[74]
			菜籽油	共9.79 g/L，有机相18.5 g/L	[84]
			OMA[Tf2N], BMIM[Tf2N]和MPPyr[Tf2N]	对照组1 g/L，OMA[Tf2N] 3 g/L，BMIM[Tf2N] 5 g/L，MPPyr[Tf2N] 3 g/L	[87]
液-固萃取	无乳状液，简单，高效	额外工作量，高成本，不易放大	将癸二酸二丁酯固定在聚乙烯聚合物基质中	共12.8 g/L，有机相20.5 g/L	[83]
液-固萃取	无乳状液，简单，高效	额外工作量，高成本，不易放大	将癸二酸二丁酯包埋于海藻酸盐基水凝胶中	共5.6 g/L，有机相47.2 g/L	[102]
疏水吸附	特异性强，操作简单，可放大，无毒，低成本，可再生	吸附容量低，缺乏吸附材料	大孔树脂	水相中2.7 g/L，每克水合树脂含84 mg 2-PE	[93]
			非极性大孔树脂D101	水相中3.15 g/L，每克树脂D101 含45.3 mg 2-PE	[65]
			树脂HZ818	水相为1.6 g/L，共6.6 g/L	[92]
			HytrelV^?8206	水相1.4 g/L，聚合物相97 g/L， 162 mg/g 2-PE	[81]
			聚甲基丙烯酸甲酯(PMMA)微球	水相为1.65 g/L，聚合物相为5.4 g/L	[103]
			颗粒活性炭	每克吸附剂182.06 mg 2-PE	[104]
有机渗透汽化	特异性强	分离能力低，成本高	聚辛基甲基硅氧烷 (POMS)膜	5.23 g/L	[60]

技术	优势	劣势	材料	2-PE产量	参考文献
超临界CO₂萃取	高效萃取力	剧毒，需要先去除细胞	超临界二氧化碳	可以提取90%以上的2-PE	[100]
液-液萃取	低成本，简单，高效，易扩展	有毒性，形成乳状液难以蒸发和去除	聚丙二醇1500	共7.5 g/L，有机相22 g/L	[82]
			聚丙二醇1200	共10.2 g/L，有机相26.5 g/L	[101]
			油酸	共12.6 g/L，有机相24 g/L	[69]
			油醇	共3.0 g/L	[74]
			菜籽油	共9.79 g/L，有机相18.5 g/L	[84]
			OMA[Tf2N], BMIM[Tf2N]和MPPyr[Tf2N]	对照组1 g/L，OMA[Tf2N] 3 g/L，BMIM[Tf2N] 5 g/L，MPPyr[Tf2N] 3 g/L	[87]
液-固萃取	无乳状液，简单，高效	额外工作量，高成本，不易放大	将癸二酸二丁酯固定在聚乙烯聚合物基质中	共12.8 g/L，有机相20.5 g/L	[83]
液-固萃取	无乳状液，简单，高效	额外工作量，高成本，不易放大	将癸二酸二丁酯包埋于海藻酸盐基水凝胶中	共5.6 g/L，有机相47.2 g/L	[102]
疏水吸附	特异性强，操作简单，可放大，无毒，低成本，可再生	吸附容量低，缺乏吸附材料	大孔树脂	水相中2.7 g/L，每克水合树脂含84 mg 2-PE	[93]
			非极性大孔树脂D101	水相中3.15 g/L，每克树脂D101 含45.3 mg 2-PE	[65]
			树脂HZ818	水相为1.6 g/L，共6.6 g/L	[92]
			HytrelV^?8206	水相1.4 g/L，聚合物相97 g/L， 162 mg/g 2-PE	[81]
			聚甲基丙烯酸甲酯(PMMA)微球	水相为1.65 g/L，聚合物相为5.4 g/L	[103]
			颗粒活性炭	每克吸附剂182.06 mg 2-PE	[104]
有机渗透汽化	特异性强	分离能力低，成本高	聚辛基甲基硅氧烷 (POMS)膜	5.23 g/L	[60]

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2-苯乙醇生物合成的研究进展

Research progress in 2-phenylethanol production through biological processes

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