Publications

• Squalene-hopene cyclases.

  Siedenburg G., Jendrossek D.

  Hopanoids and sterols are members of a large group of cyclic triterpenoic compounds that have important functions in many prokaryotic and eukaryotic organisms. They are biochemically synthesized from linear precursors (squalene, 2,3-oxidosqualene) in only one enzymatic step that is catalyzed by sq ... >> More

  Hopanoids and sterols are members of a large group of cyclic triterpenoic compounds that have important functions in many prokaryotic and eukaryotic organisms. They are biochemically synthesized from linear precursors (squalene, 2,3-oxidosqualene) in only one enzymatic step that is catalyzed by squalene-hopene cyclase (SHC) or oxidosqualene cyclase (OSC). SHCs and OSCs are related in amino acid sequences and probably are derived from a common ancestor. The SHC reaction requires the formation of five ring structures, 13 covalent bonds, and nine stereo centers and therefore is one of the most complex one-step enzymatic reactions. We summarize the knowledge of the properties of triterpene cyclases and details of the reaction mechanism of Alicyclobacillus acidocaldarius SHC. Properties of other SHCs are included. << Less

  Appl Environ Microbiol 77:3905-3915(2011) [PubMed] [EuropePMC]

  This publication is cited by 1 other entry.

• Functional characterization of triterpene synthases in <i>Cibotium barometz</i>.

  Ji Z., Fan B., Chen Y., Yue J., Chen J., Zhang R., Tong Y., Liu Z., Liang J., Duan L.

  <i>Cibotium barometz</i> (Linn.) J. Sm., a tree fern in the Dicksoniaceae family, is an economically important industrial exported plant in China and widely used in Traditional Chinese Medicine. <i>C. barometz</i> produces a range of bioactive triterpenes and their metabolites. However, the biosyn ... >> More

  <i>Cibotium barometz</i> (Linn.) J. Sm., a tree fern in the Dicksoniaceae family, is an economically important industrial exported plant in China and widely used in Traditional Chinese Medicine. <i>C. barometz</i> produces a range of bioactive triterpenes and their metabolites. However, the biosynthetic pathway of triterpenes in <i>C. barometz</i> remains unknown. To clarify the origin of diverse triterpenes in <i>C. barometz</i>, we conducted <i>de novo</i> transcriptome sequencing and analysis of <i>C. barometz</i> rhizomes and leaves to identify the candidate genes involved in <i>C. barometz</i> triterpene biosynthesis. Three <i>C. barometz</i> triterpene synthases (CbTSs) candidate genes were obtained. All of them were highly expressed in <i>C. barometz</i> rhizomes, consisting of the accumulation pattern of triterpenes in <i>C. barometz</i>. To characterize the function of these CbTSs, we constructed a squalene- and oxidosqualene-overproducing yeast chassis by overexpressing all the enzymes in the MVA pathway under the control of GAL-regulated promoter and disrupted the GAL80 gene in <i>Saccharomyces cerevisiae</i> simultaneously. Heterologous expressing CbTS1, CbTS2, and CbTS3 in engineering yeast strain produced cycloartenol, dammaradiene, and diploptene, respectively. Phylogenetic analysis revealed that CbTS1 belongs to oxidosqualene cyclase, while CbTS2 and CbTS3 belong to squalene cyclase. These results decipher enzymatic mechanisms underlying the origin of diverse triterpene in <i>C. barometz</i>. << Less

  Synth Syst Biotechnol 8:437-444(2023) [PubMed] [EuropePMC]

  This publication is cited by 2 other entries.

• The structure of the membrane protein squalene-hopene cyclase at 2.0-A resolution.

  Wendt K.U., Lenhart A., Schulz G.E.

  Squalene cyclases catalyze a cationic cyclization cascade, which is homologous to a key step in cholesterol biosynthesis. The structure of the enzyme from Alicyclobacillus acidocaldarius has been determined in a new crystal form at 2.0 A resolution (1 A=0.1 nm) and refined to an R-factor of 15.3 % ... >> More

  Squalene cyclases catalyze a cationic cyclization cascade, which is homologous to a key step in cholesterol biosynthesis. The structure of the enzyme from Alicyclobacillus acidocaldarius has been determined in a new crystal form at 2.0 A resolution (1 A=0.1 nm) and refined to an R-factor of 15.3 % (Rfree=18.7 %). The structure indicates how the initial protonation and the final deprotonation of squalene occur and how the transient carbocations are stabilized. The pathways of the flexible educt squalene from the membrane interior to the active center cavity and of the rigid fused-ring product hopene in the reverse direction are discussed. The enzyme contains eight so-called QW-sequence repeats that fortify the alpha/alpha-barrels by an intricate interaction network. They are unique to the known triterpene cyclases and are presumed to shield these enzymes against the released enthalpy of the highly exergonic catalyzed reaction. The enzyme is a monotopic membrane protein, the membrane-binding interactions of which are described and compared with those of two prostaglandin-H2 synthase isoenzymes, the only other structurally characterized proteins of this type. In the crystals the membrane-binding regions face each other, suggesting a micelle-type detergent structure between them. << Less

  J. Mol. Biol. 286:175-187(1999) [PubMed] [EuropePMC]

• Squalene hopene cyclases: highly promiscuous and evolvable catalysts for stereoselective CC and CX bond formation.

  Hammer S.C., Syren P.O., Seitz M., Nestl B.M., Hauer B.

  We review here how the inherent promiscuous nature, as well as the evolvability of terpene cyclase enzymes enables new applications in chemistry. We mainly focus on squalene hopene cyclases, class II triterpene synthases that use a proton-initiated cationic polycyclization cascade to form carbopol ... >> More

  We review here how the inherent promiscuous nature, as well as the evolvability of terpene cyclase enzymes enables new applications in chemistry. We mainly focus on squalene hopene cyclases, class II triterpene synthases that use a proton-initiated cationic polycyclization cascade to form carbopolycyclic products. We highlight recent findings to demonstrate that these enzymes are capable of activating different functionalities other than the traditional terminal isoprene C=C-group as well as being compatible with a wide range of nucleophiles beyond the 'ene-functionality'. Thus, squalene hopene cyclases demonstrate a great potential to be used as a toolbox for general Brønsted acid catalysis. << Less

  Curr Opin Chem Biol 17:293-300(2013) [PubMed] [EuropePMC]