Squalene-Hopene Cyclases

Siedenburg, Gabriele; Jendrossek, Dieter

doi:10.1128/aem.00300-11

Cited by 124 publications

(83 citation statements)

References 116 publications

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“…Studies by Wendt et al (73,74) have determined that the functional Shc enzyme is a homodimer and a cytoplasmic integral membrane protein. Although several bacterial species contain two copies of the shc gene, each seemingly of different origin, all Shc enzymes studied to date occur in bacterial species that carry only one copy of the shc gene (64). As B. cenocepacia encodes 2 different Shc proteins, it is possible that the enzyme may function as both a homodimer and a heterodimer, producing different hopanoid derivatives depending on the enzyme composition.…”

Section: Discussionmentioning

confidence: 99%

Hopanoid Production Is Required for Low-pH Tolerance, Antimicrobial Resistance, and Motility in Burkholderia cenocepacia

2011

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Hopanoids are pentacyclic triterpenoids that are thought to be bacterial surrogates for eukaryotic sterols, such as cholesterol, acting to stabilize membranes and to regulate their fluidity and permeability. To date, very few studies have evaluated the role of hopanoids in bacterial physiology. The synthesis of hopanoids depends on the enzyme squalene-hopene cyclase (Shc), which converts the linear squalene into the basic hopene structure. Deletion of the 2 genes encoding Shc enzymes in Burkholderia cenocepacia K56-2, BCAM2831 and BCAS0167, resulted in a strain that was unable to produce hopanoids, as demonstrated by gas chromatography and mass spectrometry. Complementation of the ⌬shc mutant with only BCAM2831 was sufficient to restore hopanoid production to wild-type levels, while introducing a copy of BCAS0167 alone into the ⌬shc mutant produced only very small amounts of the hopanoid peak. The ⌬shc mutant grew as well as the wild type in medium buffered to pH 7 and demonstrated no defect in its ability to survive and replicate within macrophages, despite transmission electron microscopy (TEM) revealing defects in the organization of the cell envelope. The ⌬shc mutant displayed increased sensitivity to low pH, detergent, and various antibiotics, including polymyxin B and erythromycin. Loss of hopanoid production also resulted in severe defects in both swimming and swarming motility. This suggests that hopanoid production plays an important role in the physiology of B. cenocepacia.

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Section: Discussionmentioning

confidence: 99%

Hopanoid Production Is Required for Low-pH Tolerance, Antimicrobial Resistance, and Motility in Burkholderia cenocepacia

2011

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“…Unique cyclase enzymes catalyze the different folding patterns (Phillips et al, 2006;Siedenburg and Jendrossek, 2011). From the further metabolism of these various skeletons, plants have generated some 20,000 different molecules.…”

Section: Naturally Occurring Pentacyclic Triterpenoidsmentioning

confidence: 99%

Synthetic Oleanane Triterpenoids: Multifunctional Drugs with a Broad Range of Applications for Prevention and Treatment of Chronic Disease

2012

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“…Cyclic triterpenoid lipids are synthesized by cyclization of a 30-carbon acyclic isoprenoid substrate through a series of carbocation intermediates in the central cavity of a terpene cyclase (class II) enzyme (11,22). These enzymes can be distinguished based on three general characteristics: the use of squalene or oxidosqualene as the initial substrate, the conformation of the acyclic substrate in the more energetically favorable all-chair (CCC) versus the more strained chair−boat−chair (CBC or B boat), and the total number and size of the rings generated in the final product (e.g., tetracyclic sterols versus pentacyclic hopanoids and isoarborinol) (5,7,23).…”

mentioning

confidence: 99%

Synthesis of arborane triterpenols by a bacterial oxidosqualene cyclase

Banta

Wei

Gill

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Cyclic triterpenoids are a broad class of polycyclic lipids produced by bacteria and eukaryotes. They are biologically relevant for their roles in cellular physiology, including membrane structure and function, and biochemically relevant for their exquisite enzymatic cyclization mechanism. Cyclic triterpenoids are also geobiologically significant as they are readily preserved in sediments and are used as biomarkers for ancient life throughout Earth's history. Isoarborinol is one such triterpenoid whose only known biological sources are certain angiosperms and whose diagenetic derivatives (arboranes) are often used as indicators of terrestrial input into aquatic environments. However, the occurrence of arborane biomarkers in Permian and Triassic sediments, which predates the accepted origin of angiosperms, suggests that microbial sources of these lipids may also exist. In this study, we identify two isoarborinol-like lipids, eudoraenol and adriaticol, produced by the aerobic marine heterotrophic bacterium Eudoraea adriatica. Phylogenetic analysis demonstrates that the E. adriatica eudoraenol synthase is an oxidosqualene cyclase homologous to bacterial lanosterol synthases and distinct from plant triterpenoid synthases. Using an Escherichia coli heterologous sterol expression system, we demonstrate that substitution of four amino acid residues in a bacterial lanosterol synthase enabled synthesis of pentacyclic arborinols in addition to tetracyclic sterols. This variant provides valuable mechanistic insight into triterpenoid synthesis and reveals diagnostic amino acid residues to differentiate between sterol and arborinol synthases in genomic and metagenomic datasets. Our data suggest that there may be additional bacterial arborinol producers in marine and freshwater environments that could expand our understanding of these geologically informative lipids.

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Squalene-Hopene Cyclases

Cited by 124 publications

References 116 publications

Hopanoid Production Is Required for Low-pH Tolerance, Antimicrobial Resistance, and Motility in Burkholderia cenocepacia

Hopanoid Production Is Required for Low-pH Tolerance, Antimicrobial Resistance, and Motility in Burkholderia cenocepacia

Synthetic Oleanane Triterpenoids: Multifunctional Drugs with a Broad Range of Applications for Prevention and Treatment of Chronic Disease

Synthesis of arborane triterpenols by a bacterial oxidosqualene cyclase

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