Pan Jian-Jung, Solbiati Jose O, Ramamoorthy Gurusankar, Hillerich Brandan S, Seidel Ronald D, Cronan John E, Almo Steven C, Poulter C Dale
Department of Chemistry, University of Utah, Salt Lake City, Utah 84112, United States.
Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, United States.
ACS Cent Sci. 2015;1(2):77-82. doi: 10.1021/acscentsci.5b00115.
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-, , , and -for conversion of farnesyl diphosphate (FPP) to hopene or related pentacyclic metabolites. While is known to encode a squalene cyclase, the functions for , , and are not rigorously established. The , , and genes from and were cloned into , a bacterium that does not contain genes homologous to , , and , and their functions were established and . 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.
角鲨烯（SQ）是真核生物和少数细菌中甾醇生物合成的中间体，也是细菌中藿烷类化合物生物合成的中间体，在细菌中它们可促进宿主细胞膜的稳定性和脂筏的形成。藿烷类化合物生物合成的基因通常位于由四个高度保守的基因（、、和）组成的基因簇上，这些基因负责将法尼基二磷酸（FPP）转化为藿烯或相关的五环代谢产物。虽然已知编码角鲨烯环化酶，但、和的功能尚未得到严格证实。将来自和的、和基因克隆到中，是一种不含有与、和同源基因的细菌，并确定了它们的功能。HpnD催化由两分子FPP形成前角鲨烯二磷酸（PSPP）；HpnC将PSPP转化为羟基角鲨烯（HSQ）；HpnE是胺氧化还原酶家族的成员，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。
