FATTY-ACID MONOOXYGENATION BY P450BM-3 - PRODUCT IDENTIFICATION AND PROPOSED MECHANISMS FOR THE SEQUENTIAL HYDROXYLATION REACTIONS
FATTY-ACID MONOOXYGENATION BY P450BM-3 - PRODUCT IDENTIFICATION AND PROPOSED MECHANISMS FOR THE SEQUENTIAL HYDROXYLATION REACTIONS
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DOI：
10.1016/0003-9861(92)90045-x
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发表时间：
1992-01-01
影响因子：
3.9
通讯作者：
PETERSON, JA
中科院分区：
文献类型：
--
作者：
BODDUPALLI, SS;PRAMANIK, BC;PETERSON, JA
从巨型芽孢杆菌（bacillus megaterium）中分离到的可溶性P450 （cyp102基因的产物）（P450BM-3）是一种催化自给自足的脂肪酸羟化酶，可将月桂酸、肉豆蔻酸和棕榈酸转化为ω-1、ω-2和ω-3羟基类似物。区域异构体的百分比分布取决于底物链的长度。月桂酸和肉豆蔻酸优先代谢为ω-1羟基，而以癸酸为底物时没有发生羟基化。当浓度大于反应介质中氧的浓度（>250 μm）时，棕榈酸羟基化成ω-1、ω-2和ω-3羟基类似物，其区域异构体的百分比分布分别为21:44:35。没有检测到任何脂肪酸的ω羟基化。当棕榈酸的浓度小于反应混合物中氧的浓度时，注意到形成了一些额外的产物。在这些条件下，与月桂酸和肉豆汁酸不同，棕榈酸首先转化为单羟基异构体，随后代谢为14-酮十六酸、15-酮十六酸、13-羟基-14-酮十六酸、14-羟基-15-酮十六酸和13,14-二羟基十六酸的混合物，相对分布分别为8:2:40:30:20。因此，p450bm -3不仅能够将多种脂肪酸单羟基化，而且还能够将其中一些初级代谢物进一步代谢为二级和三级产物。本文描述了棕榈酸连续羟基化过程中形成的产物，并提出了解释这些结果的反应途径。
The soluble P450 isolated fromBacillus megaterium(the product of theCYP102 gene) (P450BM-3) is a catalytically self-sufficient fatty acid hydroxylase which converts lauric, myristic, and palmitic acids to ω-1, ω-2, and ω-3 hydroxy analogs. The percentage distribution of the regioisomers depends on the substrate chain length. Lauric and myristic acids were preferentially metabolized to their ω-1 hydroxy counterparts while no hydroxylation occurred when capric acid was used as the substrate. Palmitic acid, when present at concentrations greater than the concentration of oxygen in the reaction medium (>250 μm), was hydroxylated to its ω-1, ω-2, and ω-3 hydroxy analogs, with the percentage distribution of the regioisomers being 21:44:35, respectively. No ω hydroxylation of any of the fatty acids was detected. When the concentration of palmitic acid was less than the concentration of oxygen in the reaction mixture, it was noted that a number of additional products were formed. Under these conditions, unlike lauric and myristic acids, it was observed that palmitic acid was first converted to its monohydroxy isomers which were subsequently metabolized to a mixture of 14-ketohexadecanoic, 15-ketohexadecanoic, 13-hydroxy-14-ketohexadecanoic, 14-hydroxy-15-ketohexadecanoic, and 13,14-dihydroxyhexadecanoic acids with a relative distribution of 8:2:40:30:20, respectively. Thus, P450BM-3is able not only to monohydroxylate a variety of fatty acids but also to further metabolize some of these primary metabolites to secondary and tertiary products. The present paper characterizes the products formed during the sequential hydroxylation of palmitic acid and proposes reaction pathways to explain these results.