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Biosynthesis of Squalene from Farnesyl Diphosphate in Bacteria: Three Steps Catalyzed by Three Enzymes
ACS Central Science ( IF 12.7 ) Pub Date : 2015-04-20 00:00:00 , DOI: 10.1021/acscentsci.5b00115
Jian-Jung Pan 1 , Jose O. Solbiati 2 , Gurusankar Ramamoorthy 1 , Brandan S. Hillerich 3 , Ronald D. Seidel 3 , John E. Cronan 4 , Steven C. Almo 3 , C. Dale Poulter 1
Affiliation  

Squalene (SQ) is an intermediate in the biosynthesis of sterols in eukaryotes and a few bacteria and of hopanoids in bacteria where they promote membrane stability and the formation of lipid rafts in their hosts. The genes for hopanoid biosynthesis are typically located on clusters that consist of four highly conserved genes—hpnC, hpnD, hpnE, and hpnF—for conversion of farnesyl diphosphate (FPP) to hopene or related pentacyclic metabolites. While hpnF is known to encode a squalene cyclase, the functions for hpnC, hpnD, and hpnE are not rigorously established. The hpnC, hpnD, and hpnE genes from Zymomonas mobilis and Rhodopseudomonas palustris were cloned into Escherichia coli, a bacterium that does not contain genes homologous to hpnC, hpnD, and hpnE, and their functions were established in vitro and in vivo. HpnD catalyzes formation of presqualene diphosphate (PSPP) from two molecules of FPP; HpnC converts PSPP to hydroxysqualene (HSQ); and HpnE, a member of the amine oxidoreductase family, reduces HSQ to SQ. Collectively the reactions catalyzed by these three enzymes constitute a new pathway for biosynthesis of SQ in bacteria.

中文翻译:

法尼基二磷酸酯在细菌中生物合成角鲨烯:三种酶催化的三个步骤

角鲨烯(SQ)是真核生物中固醇和一些细菌以及细菌中类hopanoids生物合成的中间体,它们在它们的宿主中促进膜的稳定性和脂质筏的形成。拟南芥生物合成的基因通常位于由四个高度保守的基因(hpnChpnDhpnEhpnF)组成的簇上,用于将法呢基二磷酸酯(FPP)转化为戊烯或相关的五环代谢物。尽管已知hpnF编码角鲨烯环化酶,但尚未严格建立hpnChpnDhpnE的功能。该hpnChpnD来自运动发酵单胞菌红假单胞菌的hpnE基因被克隆到大肠杆菌中,该细菌不包含与hpnChpnDhpnE同源的基因,并在体内体外建立它们的功能。HpnD催化由两个FPP分子形成角鲨烯二磷酸(PSPP)。HpnC将PSPP转换为羟基角鲨烯(HSQ);胺氧化还原酶家族的成员HpnE将HSQ还原为SQ。这三种酶催化的反应共同构成了细菌中SQ生物合成的新途径。
更新日期:2015-04-20
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