Volodina Elena, Steinbüchel Alexander
Institut für Molekulare Mikrobiologie und Biotechnologie, Westfälische Wilhelms-Universität Münster, Corrensstraße 3, Münster, D-48149, Germany.
Institut für Molekulare Mikrobiologie und Biotechnologie, Westfälische Wilhelms-Universität Münster, Corrensstraße 3, Münster, D-48149, Germany ; King Abdulaziz University, Jeddah, Saudi Arabia.
AMB Express. 2014 Aug 28;4:69. doi: 10.1186/s13568-014-0069-0. eCollection 2014.
In this study (S)-3-hydroxyacyl-CoA dehydrogenase/enoyl-CoA hydratase (H16_A0461/FadB', gene ID: 4247876) from one of two active fatty acid degradation operons of Ralstonia eutropha H16 has been heterologously expressed in Escherichia coli, purified as protein possessing a His-Tag and initially characterized. FadB' is an enzyme with two catalytic domains exhibiting a single monomeric structure and possessing a molecular weight of 86 kDa. The C-terminal part of the enzyme harbors enoyl-CoA hydratase activity and is able to convert trans-crotonyl-CoA to 3-hydroxybutyryl-CoA. The N-terminal part of FadB' comprises an NAD(+) binding site and is responsible for 3-hydroxyacyl-CoA dehydrogenase activity converting (S)-3-hydroxybutyryl-CoA to acetoacetyl-CoA. Enoyl-CoA hydratase activity was detected spectrophotometrically with trans-crotonyl-CoA. (S)-3-Hydroxyacyl-CoA dehydrogenase activity was measured in both directions with acetoacetyl-CoA and 3-hydroxybutyryl-CoA. FadB' was found to be strictly stereospecific to (S)-3-hydroxybutyryl-CoA and to prefer NAD(+). The K m value for acetoacetyl-CoA was 48 μM and V max 149 μmol mg(-1) min(-1). NADP(H) was utilized at a rate of less than 10% in comparison to activity with NAD(H). FadB' exhibited optimal activity at pH 6-7 and the activity decreased at alkaline and acidic pH values. Acetyl-CoA, propionyl-CoA and CoA were found to have an inhibitory effect on FadB'. This study is a first report on biochemical properties of purified (S)-stereospecific 3-hydroxyacyl-CoA dehydrogenase/enoyl-CoA hydratase with the inverted domain order from R. eutropha H16. In addition to fundamental information about FadB' and fatty acid metabolism, FadB' might be also interesting for biotechnological applications.
在本研究中,来自真养产碱菌H16两个活性脂肪酸降解操纵子之一的(S)-3-羟酰基辅酶A脱氢酶/烯酰辅酶A水合酶(H16_A0461/FadB',基因ID:4247876)已在大肠杆菌中进行了异源表达,纯化得到带有His标签的蛋白质,并进行了初步表征。FadB'是一种具有两个催化结构域的酶,呈单一单体结构,分子量为86 kDa。该酶的C端部分具有烯酰辅酶A水合酶活性,能够将反式巴豆酰辅酶A转化为3-羟基丁酰辅酶A。FadB'的N端部分包含一个NAD(+)结合位点,负责将(S)-3-羟基丁酰辅酶A转化为乙酰乙酰辅酶A的3-羟酰基辅酶A脱氢酶活性。用反式巴豆酰辅酶A通过分光光度法检测烯酰辅酶A水合酶活性。用乙酰乙酰辅酶A和3-羟基丁酰辅酶A双向测定(S)-3-羟酰基辅酶A脱氢酶活性。发现FadB'对(S)-3-羟基丁酰辅酶A具有严格的立体特异性,且更倾向于NAD(+)。乙酰乙酰辅酶A的K m值为48 μM,V max为149 μmol mg(-1) min(-1)。与NAD(H)的活性相比,NADP(H)的利用率不到10%。FadB'在pH 6-7时表现出最佳活性,在碱性和酸性pH值下活性降低。发现乙酰辅酶A、丙酰辅酶A和辅酶A对FadB'有抑制作用。本研究首次报道了来自真养产碱菌H16的具有反向结构域顺序的纯化的(S)-立体特异性3-羟酰基辅酶A脱氢酶/烯酰辅酶A水合酶的生化特性。除了关于FadB'和脂肪酸代谢的基础信息外,FadB'在生物技术应用方面可能也很有意义。