Production of human milk fat substitute by engineered strains of Yarrowia lipolytica.
Production of human milk fat substitute by engineered strains of Yarrowia lipolytica.
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DOI：
10.1016/j.mec.2022.e00192
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发表时间：
2022-06
影响因子：
5.2
通讯作者：
Eastmond PJ
中科院分区：
文献类型：
--
作者：
Bhutada G;Menard G;Bhunia RK;Hapeta PP;Ledesma-Amaro R;Eastmond PJ
人乳脂具有独特的立体异构体结构，其中棕榈酸被酯化到三酰基甘油骨架上的中间（sn-2）位置，不饱和脂肪酸被酯化到外侧（sn-1/3）位置。这种结构允许婴儿肠道更有效地吸收营养。然而，大多数婴儿配方奶粉中使用的脂肪来自植物，这就排除了sn-2位置的棕榈酸。产油酵母为人类营养提供了另一种脂质来源。然而，这些酵母也从其三酰甘油的sn-2位置排除棕榈酸。本研究表明，通过表达具有棕榈酰基辅酶A特异性的溶血磷脂酸酰基转移酶，可以对聚脂耶氏菌进行工程改造，使其以超过60%的棕榈酸在n-2位置产生三酰基甘油。在氮限制条件下，在甘油、葡萄糖、棕榈油或混合底物上培养的工程解脂芽孢杆菌菌株可以产生三酰基甘油，其脂肪酸组成类似于主要分子种类（棕榈酸、油酸和亚油酸）的人乳脂肪。在棕榈油或葡萄糖和棕榈油混合物上培养产生最高的脂质滴度和与人乳脂最相似的三酰基甘油组成。我们的数据表明，一种产油酵母可以被改造成一种人类乳脂替代品（β-棕榈酸酯），可以用作婴儿配方奶粉的一种成分。解脂耶氏菌是用来制造人类乳脂替代品的。通过表达莱茵衣藻LPAAT2，将棕榈酸酯定向到甘油三酯的sn-2位置。棕榈油培养产生的脂肪酰基组成与人类乳脂更相似。
Human milk fat has a distinctive stereoisomeric structure where palmitic acid is esterified to the middle (sn-2) position on the glycerol backbone of the triacylglycerol and unsaturated fatty acids to the outer (sn-1/3) positions. This configuration allows for more efficient nutrient absorption in the infant gut. However, the fat used in most infant formulas originates from plants, which exclude palmitic acid from the sn-2 position. Oleaginous yeasts provide an alternative source of lipids for human nutrition. However, these yeasts also exclude palmitic acid from the sn-2 position of their triacylglycerol. Here we show that Yarrowia lipolytica can be engineered to produce triacylglycerol with more than 60% of the palmitic acid in the sn-2 position, by expression of lysophosphatidic acid acyltransferases with palmitoyl-Coenzyme A specificity. The engineered Y. lipolytica strains can be cultured on glycerol, glucose, palm oil or a mixture of substrates, under nitrogen limited condition, to produce triacylglycerol with a fatty acid composition that resembles human milk fat, in terms of the major molecular species (palmitic, oleic and linoleic acids). Culture on palm oil or a mixture of glucose and palm oil produced the highest lipid titre and a triacylglycerol composition that is most similar with human milk fat. Our data show that an oleaginous yeast can be engineered to produce a human milk fat substitute (β-palmitate), that could be used as an ingredient in infant formulas. Yarrowia lipolytica was engineered to make a human milk fat substitute. Palmitate was directed to the sn-2 position of triacylglycerol by expressing Chlamydomonas reinhardtii LPAAT2. Culture with palm oil produced a fatty acyl composition more similar with human milk fat.
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影响因子：
3.3
作者：
Braunwald, Teresa;French, William Todd;Graeff-Hoenninger, Simone
通讯作者：
Graeff-Hoenninger, Simone
影响因子：
48
作者：
Gibson, Daniel G.;Young, Lei;Smith, Hamilton O.
通讯作者：
Smith, Hamilton O.
影响因子：
7.4
作者：
Bates, Philip D.;Fatihi, Abdelhak;Lu, Chaofu
通讯作者：
Lu, Chaofu
DOI：
10.1016/0005-2760(70)90060-3
发表时间：
1970-01-01
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
CHRISTIE, WW;MOORE, JH
通讯作者：
MOORE, JH
影响因子：
6.3
作者：
Beghin, Laurent;Marchandise, Xavier;Turck, Dominique
通讯作者：
Turck, Dominique