中国农业大学食品科学与营养工程学院,北京 100083
[ "史然(1987—),女,博士研究生,研究方向为食品酶的发掘与应用。E-mail:shiranb20153060234@cau.edu.cn" ]
[ "江正强(1971—),男,博士生导师,教授,研究方向为食品酶与发酵工程。E-mail:zhqjiang@cau.edu.cn" ]
收稿:2020-03-23,
修回:2020-05-09,
纸质出版:2020-08-31
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史然, 江正强. 2'-岩藻糖基乳糖的酶法合成研究进展和展望[J]. 合成生物学, 2020, 1(4): 481-494
SHI Ran, JIANG Zhengqiang. Enzymatic synthesis of 2'-fucosyllactose: advances and perspectives[J]. Synthetic Biology Journal, 2020, 1(4): 481-494
史然, 江正强. 2'-岩藻糖基乳糖的酶法合成研究进展和展望[J]. 合成生物学, 2020, 1(4): 481-494 DOI: 10.12211/2096-8280.2020-033.
SHI Ran, JIANG Zhengqiang. Enzymatic synthesis of 2'-fucosyllactose: advances and perspectives[J]. Synthetic Biology Journal, 2020, 1(4): 481-494 DOI: 10.12211/2096-8280.2020-033.
人乳寡糖(human milk oligosaccharides,HMOs)是人乳中一类结构复杂、非消化性的碳水化合物。2
'-
岩藻糖基乳糖(2
'
-fucosyllactose,2
'
-FL)是人乳中含量最高的寡糖,也是最早被FDA和欧盟批准可添加到婴幼儿奶粉、膳食补充剂以及医疗食品中的HMOs之一。2
'
-FL具有调节肠道菌群、抵抗病原菌的黏附、免疫调节及促进神经系统发育和修复等多种功能活性。2
'
-FL的主要合成方法有化学合成法、全细胞合成法及酶催化合成法。全细胞合成法是当前工业上生产2
'
-FL的主要方法,降低L-岩藻糖的成本、调节合成途径中鸟苷二磷酸-L-岩藻糖(GDP-岩藻糖)的水平与菌体生长之间的平衡、发掘新型高活性的
α
-1,2-岩藻糖基转移酶是降低全细胞合成2
'
-FL成本的关键。2
'
-FL的合成途径在一些更为安全表达宿主(如无抗生素大肠杆菌、枯草芽孢杆菌和酵母菌等)中的构建也面临着挑战。本文重点综述了2
'
-FL酶法合成的研究现状,利用
α
-1,2-岩藻糖基转移酶合成2
'
-FL专一性好,但所需糖基供体GDP-岩藻糖成本较高;利用
α
-L-岩藻糖苷酶的转糖苷活性也可以合成2
'
-FL,
α
-L-岩藻糖苷酶来源广泛,易获得,稳定性好,可利用天然底物作为糖基供体。将
α
-L-岩藻糖苷酶应用于2
'
-FL合成的关键在于高效的转糖苷酶以及天然、经济的岩藻糖基供体的发掘。酶法合成将来有望成为工业上生产2
'
-FL的方法。
Human milk oligosaccharides (HMOs) constitute a unique group of endogenous indigestible carbohydrates in human breast milk. HMOs play a crucial role in infant health and growth. As the most abundant HMO
2'-fucosyllactose (Fucα1
2Galβ1
4Glc
2'-FL) has been approved for infant formulas
dietary supplements and medical foods in the United States and European Union. 2'-FL has been synthesized by chemical
enzymatic synthesis and cell factory approaches
and currently mainly produced by cell factory approach. The crucial factors for 2'-FL production are the reduction of the cost of L-fucose
the discovery of novel α1
2-fucosyltransferases
and the maintenance of the balance between intracellular GDP-L-fucose level and the growth of engineering strain. Also
the construction of antibiotic-free system (such as antibiotic-free
Escherichia coli
Bacillus subtilis
and
Saccharomyces cerevisiae
) is still a challenge for the synthesis of 2'-FL. In this review
the research progress of enzymatic synthesis of 2'-FL was particularly presented. 2'-FL could be enzymatically synthesized using α-1
2-fucosyltransferases or α-L-fucosidases. α-1
2-Fucosyltransferases catalyze the transformation of a fucose from a GDP-L-fucose to a lactose. The main disadvantage for 2'-FL synthesis by fucosyltransferase is the requirement for an expensive nucleotide donor. Also
α-L-fucosidases have been studied extensively since they catalyze the synthesis of 2'-FL through a transglycosylation reaction and often possess a higher availability and activity
in comparison with fucosyltransferases. The discovery of efficient transfucosidases and the availability of appropriate
fucosylated donor substrates will promote the application of α-L-fucosidases in the synthesis
of 2'-FL. In the near future
enzymatic synthesis is expected to become a method for industrial production of 2'-FL.
2
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