Hopanoids - Knowledge

572: 363: 20: 346: 3409: 897:, a drug-resistance mechanism mediated by integral transport proteins, lost the ability to perform both multidrug transport and hopanoid synthesis. Researchers indicate this could be due to direct regulation of transport proteins by hopanoids or indirectly by altering membrane ordering in a way that disrupts the transport system. 745:

has furthered a non-cyanobacterial explanation for the observed abundance of 2-methylhopanes associated with Cretaceous OAEs. Felix Elling and colleagues propose that overturning circulation brought ammonia- and cobalt-rich deep waters to the surface, promoting aerobic nitrite oxidation and cobalamin

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and eukaryotic organisms such as lichens and bryophytes have been shown to produce both sterols and hopanoids, suggesting these lipids may have other distinct functions. Notably, the way hopanoids pack into the plasma membrane can change depending on what functional groups are attached. The hopanoid

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The application of hopanoids and hopanoid-producing nitrogen fixers to soil has been proposed and patented as a biofertilizer technique that increases environmental resistance of plant-associated microbial symbionts, including nitrogen-fixing bacteria that are essential for transforming atmospheric

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Some representative hopanoids: A. Diploptene, also called 22(29)-hopene B. Diplopterol, also called hopan-22-ol, the hydrated cyclomer of diploptene C. Bacteriohopanetetrol (BHT), a common extended hopanoid D. Hopane, the diagenetic product of A and B that results from reducing conditions during

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during sterol biosynthesis. Furthermore, squalene binds to squalene-hopene cyclases in a low-energy, all-chair conformation while oxidosqualene is cyclized in a more strained, chair-boat-chair-boat conformation. Squalene-hopene cyclases also display more substrate promiscuity in that they cyclize

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Hopanoids have been estimated to be the most abundant natural products on Earth, remaining in the organic fraction of all sediments, independent of age, origin or nature. The total amount in the Earth was estimated as 10 x 10 gram (10 ton) in 1992. Biomolecules like DNA and proteins are degraded

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and monolayers of glycan-modified lipid A. Furthermore, both diplopterol and cholesterol could rescue pH-dependent phase transitions in glycan-modified lipid A monolayers. The role of hopanoids in membrane-mediated acid tolerance is further supported by observations of acid-inhibited growth and

555:, causing some scientists to hypothesize that they are evolutionary predecessors to oxidosqualene cyclases. Other scientists have proposed that squalene-hopene and oxidosqualene cyclases diverged from a common ancestor, a putative bacterial cyclase that would have made a tricyclic 374:

Next, a squalene-hopene cyclase catalyzes an elaborate cyclization reaction, engaging squalene in an energetically favorable all-chair conformation before creating 5 cycles, 6 covalent bonds, and 9 chiral centers on the molecule in a single step. This enzyme, coded for by the gene

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from adenosylhopane to make ribosyl hopane, which reacts to form bacteriohopanetetrol (BHT) in a reaction mediated by an unknown enzyme. Additional modifications may occurs as HpnO aminates the terminal hydroxyl on BHT, producing amino bacteriohopanetriol, or as the

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The elegant mechanism behind the protonase activity of squalene-hopene cyclase was appreciated and adapted by chemical engineers at the University of Stuttgart, Germany. Active site engineering resulted in loss of the enzyme's ability to form hopanoids, but enabled

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carbocation formed during polycyclization. This indicates that hopanoids can be made without molecular oxygen and could have served as a sterol surrogate before the atmosphere accumulated oxygen, which reacts with squalene in a reaction catalyzed by

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carbocation may be quenched by mechanisms that lead to different hopanoid products. Nucleophilic attack of water will yield diplopterol, while deprotonation at an adjacent carbon will form one of several hopene isomers, often diploptene.

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as it condenses two molecules of FPP to PSPP, which HpnC converts to hydroxysqualene, consuming a water molecule and releasing another pyrophosphate. Then, hydroxysqualene is reduced to squalene in a dehydration reaction mediated by the

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based on culture experiments and co-occurrence with aerobic methanotrophs in the environment. As such, the presence of 3-methylhopanes, together with C depletion, are considered markers of ancient aerobic methanotrophy. However,

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Perzl M, Reipen IG, Schmitz S, Poralla K, Sahm H, Sprenger GA, Kannenberg EL (July 1998). "Cloning of conserved genes from Zymomonas mobilis and Bradyrhizobium japonicum that function in the biosynthesis of hopanoid lipids".

66:, a natural resin used as a varnish for paintings. While hopanoids are often assumed to be made only in bacteria, their name actually comes from the abundance of hopanoid compounds in the resin of plants from the genus 700:

Among cyanobacteria, hopanoid production is generally limited to terrestrial cyanobacteria. Among marine cyanobacteria, culture experiments in conducted by Helen Talbot and colleagues concluded that only two marine

3407:, Newman DK, Kulkarni G, Belin BJ, "Hopanoids producing bacteria and related biofertilizers, compositions, methods and systems", issued 2016-10-19, assigned to California Institute of Technology 2862:

French, Katherine L.; Hallmann, Christian; Hope, Janet M.; Schoon, Petra L.; Zumberge, J. Alex; Hoshino, Yosuke; Peters, Carl A.; George, Simon C.; Love, Gordon D.; Brocks, Jochen J.; Buick, Roger (2015-05-12).

727:. These cold- and desiccation-resistant cell structures are dormant and therefore not photosynthetically active, further challenging the association between 2-methylhopanes and oxygenic photosynthesis. 541:

For several reasons, hopanoids and squalene-hopene cyclases have been hypothesized to be more ancient than sterols and oxidosqualene cyclases. First, diplopterol is synthesized when water quenches the C

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HpnI converts BHT to N-acetylglucosaminyl-BHT. In sequence, the hopanoid biosynthesis associated protein HpnK mediates deacetylation to glucosaminyl-BHT, from which radical SAM protein HpnJ generates a

624:(million year) gap between the evolution of oxygenic metabolism and the Great Oxidation Event. However, these findings were later rejected due to potential contamination by modern hydrocarbons. 3138:

Talbot HM, Summons RE, Jahnke LL, Cockell CS, Rohmer M, Farrimond P (2008-02-01). "Cyanobacterial bacteriohopanepolyol signatures from cultures and natural environmental settings".

3289:"Prokaryotic triterpenoids. 3. The biosynthesis of 2beta-methylhopanoids and 3beta-methylhopanoids of Methylobacterium organophilum and Acetobacter pasteurianus ssp. pasteurianus" 719:(MAGs) drew similar conclusions, identifying the gene in ~30% of terrestrial and freshwater species, and only one of the 739 marine cyanobacterial genomes and MAGs. Additionally, 2571:

Brocks JJ, Love GD, Summons RE, Knoll AH, Logan GA, Bowden SA (October 2005). "Biomarker evidence for green and purple sulphur bacteria in a stratified Palaeoproterozoic sea".

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Fischer WW, Summons RE, Pearson A (2005). "Targeted genomic detection of biosynthetic pathways: anaerobic production of hopanoid biomarkers by a common sedimentary microbe".

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An environmental survey by Jessica Ricci and coauthors using metagenomes and clone libraries found significant correlation between plant-associated microbial communities and

508:, but polycyclic lipids persist in the environment over geologic timescales due to their fused, stable structures. Although hopanoids and sterols are reduced to hopanes and 681:

was found to produce 2-methyl-BHPs only under anoxic conditions. This latter discovery also lead to the identification of the gene encoding the key methyltransferase HpnP.

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In a biosynthetic pathway exclusive to some bacteria, the enzyme tetrahymanol synthase catalyzes the conversion of the hopanoid diploptene to the pentacyclic triterpenoid

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presence, based on which they propose that 2-methylhopanoids are a biomarker for sessile microbial communities high in osmolarity and low in oxygen and fixed nitrogen.

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HpnP and HpnR, respectively. These two methylations are particularly geostable compared to side-chain modifications and have entertained geobiologists for decades.

2965:"Lipid biomarker stratigraphic records through the Late Devonian Frasnian/Famennian boundary: Comparison of high- and low-latitude epicontinental marine settings" 3369:

Hammer SC, Marjanovic A, Dominicus JM, Nestl BM, Hauer B (February 2015). "Squalene hopene cyclases are protonases for stereoselective Brønsted acid catalysis".

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was demonstrated to synthesize diverse hopanols, although not 2-methyl-hopanols, when grown under strictly anaerobic conditions. Furthermore, the anoxygenic

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Tippelt A, Jahnke L, Poralla K (March 1998). "Squalene-hopene cyclase from Methylococcus capsulatus (Bath): a bacterium producing hopanoids and steroids".

2999:"Molecular and petrographic indicators of redox conditions and bacterial communities after the F/F mass extinction (Kowala, Holy Cross Mountains, Poland)" 1100:

William W. Christie. "The AOCS Lipid Library. Hopanoids". American Oil Chemists' Society. Archived from the original on 2016-03-05. Retrieved 2015-11-17.

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interact in eukaryotic plasma membranes. Diplopterol and cholesterol were demonstrated to promote condensation and inhibit gel-phase formation in both

2242:"Elucidation of the Burkholderia cenocepacia hopanoid biosynthesis pathway uncovers functions for conserved proteins in hopanoid-producing bacteria" 3089: 329:. However, some hopanoid-producing bacteria lack squalene synthase and instead use the three enzymes HpnC, HpnD and HpnE, which are encoded in the 404:

on the substrate which are quenched by a rapid polycyclization. In the last substep of the cyclization reaction, after electrons comprising the

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operon with many other hopanoid biosynthesis genes. In this alternative yet seemingly more widespread squalene synthesis pathway, HpnD releases

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Haddad, Emily E.; Tuite, Michael L.; Martinez, Aaron M.; Williford, Kenneth; Boyer, Diana L.; Droser, Mary L.; Love, Gordon D. (August 2016).

1110: 236:, hopanoids chemically bonded to lipid A increase membrane stability and rigidity, enhancing stress tolerance and intracellular survival in 3227:

Ricci, Jessica N; Coleman, Maureen L; Welander, Paula V; Sessions, Alex L; Summons, Roger E; Spear, John R; Newman, Dianne K (March 2014).

689:, and phylogenetic analysis of the gene concluded that it originated in the alphaproteobacteria and was acquired by the cyanobacteria and 3168:

Elling, Felix J.; Hemingway, Jordon D.; Evans, Thomas W.; Kharbush, Jenan J.; Spieck, Eva; Summons, Roger E.; Pearson, Ann (2020-12-29).

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Structure of a 2-α-methylhopane with the carbons of the base hopane structure numbered according to convention. The methyl group at the C

322: 893:, multidrug transport was found to be a hopanoid-dependent process. Squalene-hopene cyclase mutants derived from a wild type capable of 2295:"Identification of a methylase required for 2-methylhopanoid production and implications for the interpretation of sedimentary hopanes" 2686:

Ourisson G, Albrecht P, Rohmer M (1982-07-01). "Predictive microbial biochemistry — from molecular fossils to procaryotic membranes".

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Syrén PO, Henche S, Eichler A, Nestl BM, Hauer B (December 2016). "Squalene-hopene cyclases-evolution, dynamics and catalytic scope".

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Poger D, Mark AE (December 2013). "The relative effect of sterols and hopanoids on lipid bilayers: when comparable is not identical".

174:. Although hopanoids do not rescue sterol deficiency, they are thought to increase membrane rigidity and decrease permeability. Also, 2161:

Bradley AS, Pearson A, Sáenz JP, Marx CJ (2010-10-01). "Adenosylhopane: The first intermediate in hopanoid side chain biosynthesis".

495:, tetrahymanol is instead synthesized directly from squalene by a cyclase with no homology to the bacterial tetrahymanol synthase. 314: 627:

Putative cyanobacterial presence on the basis of abundant 2-methylhopanes has been used to explain black shale deposition during

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in some bacteria), has a double ⍺-barrel fold characteristic of terpenoid biosynthesis and is present in the cell as a monotopic

3170:"Vitamin B 12 -dependent biosynthesis ties amplified 2-methylhopanoid production during oceanic anoxic events to nitrification" 47:

molecules therefore refers to simple hopenes, hopanols and hopanes, but also to extensively functionalized derivatives such as

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After cyclization, hopanoids are frequently modified by hopanoid biosynthesis enzymes encoded by genes in the same operon as

183:, but diploptene localizes between the inner and outer leaflet, presumably thickening the membrane to decrease permeability. 2996:

Marynowski, Leszek; Rakociński, Michał; Borcuch, Ewelina; Kremer, Barbara; Schubert, Brian A.; Jahren, A. Hope (June 2011).

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depending on the bacterial species, although the latter tends to be more common. DMAP condenses with one molecule of IPP to

2241: 1480:"Hopanoid production is required for low-pH tolerance, antimicrobial resistance, and motility in Burkholderia cenocepacia" 666:

The status of 2-methylhopanoids as a cyanobacterial biomarker was challenged by a number of microbiological discoveries.

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morphological abnormalities of the plasma membrane in hopanoid-deficient bacteria with mutant squalene-hopene cyclases.

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Gold DA, Caron A, Fournier GP, Summons RE (March 2017). "Paleoproterozoic sterol biosynthesis and the rise of oxygen".

2359:"Discovery, taxonomic distribution, and phenotypic characterization of a gene required for 3-methylhopanoid production" 2190:"Ribosylhopane, a novel bacterial hopanoid, as precursor of C35 bacteriohopanepolyols in Streptomyces coelicolor A3(2)" 1047:

Volkman JK (2005-02-01). "Sterols and other triterpenoids: source specificity and evolution of biosynthetic pathways".

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Ourisson G, Albrecht P (September 1992). "Hopanoids. 1. Geohopanoids: the most abundant natural products on Earth?".

3339:"Occurrence of unusual steroids and hopanoids derived from aerobic methanotrophs at an active marine mud volcano" 2922:

Kuypers, Marcel M.M.; van Breugel, Yvonne; Schouten, Stefan; Erba, Elisabetta; Sinninghe Damsté, Jaap S. (2004).

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analyses estimate that the earliest sterols were likely produced around 2.3 Ga ago, around the same time as the

1640:"Covalently linked hopanoid-lipid A improves outer-membrane resistance of a Bradyrhizobium symbiont of legumes" 789:

have been known for decades to also produce 2-methylhopanoids. Additionally, following their identification of

2045:"Site-directed mutagenesis of squalene-hopene cyclase: altered substrate specificity and product distribution" 1581:"Hopanoid lipids compose the Frankia vesicle envelope, presumptive barrier of oxygen diffusion to nitrogenase" 1977:

Hoshino T, Sato T (February 2002). "Squalene-hopene cyclase: catalytic mechanism and substrate recognition".

321:, then catalyzes the condensation of two FPP molecules to presqualene pyrophosphate (PSPP) before oxidizing 746:

synthesis, respectively. This model also addresses the conspicuous lack of 2-methylhopanes associated with

59: 3404: 1741:"Hopanoids are formed during transition from substrate to aerial hyphae in Streptomyces coelicolor A3(2)" 889: 757:

sediments. Because both environments feature much less upwelling, 2-methylhopanoid-producing NOB such as

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for the presence of specific microbes and potentially for chemical or physical conditions at the time of

3090:"Phylogenetic analysis of HpnP reveals the origin of 2-methylhopanoid production in Alphaproteobacteria" 2721:

Fischer WW, Pearson A (2007). "Hypotheses for the origin and early evolution of triterpenoid cyclases".

1826:"Biosynthesis of Squalene from Farnesyl Diphosphate in Bacteria: Three Steps Catalyzed by Three Enzymes" 1692:"2-Methylhopanoids are maximally produced in akinetes of Nostoc punctiforme: geobiological implications" 593:

2-methylhopanes, often quantified as the 2-α-methylhopane index, were first proposed as a biomarker for

2924: 677: 571: 254:, large quantities of 2-methylhopanoids localize to the outer membranes of survival structures called 3434: 2086:"Non-specific biosynthesis of hopane triterpenes by a cell-free system from Acetobacter pasteurianum" 286: 2505:

Summons RE, Lincoln SA (2012-03-30). "Biomarkers: Informative Molecules for Studies in Geobiology".

1532:"Hopanoids play a role in membrane integrity and pH homeostasis in Rhodopseudomonas palustris TIE-1" 1114: 694: 668: 655: 206: 1824:

Pan JJ, Solbiati JO, Ramamoorthy G, Hillerich BS, Seidel RD, Cronan JE, et al. (2015-05-27).

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Silipo A, Vitiello G, Gully D, Sturiale L, Chaintreuil C, Fardoux J, et al. (October 2014).

152: 1295:"Methylation at the C-2 position of hopanoids increases rigidity in native bacterial membranes" 1074:

Hunt JM, Philp RP, Kvenvolden KA (2002-09-01). "Early developments in petroleum geochemistry".

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Since hopanoids modify plasma membrane properties in bacteria, they are frequently compared to

3229:"Diverse capacity for 2-methylhopanoid production correlates with a specific ecological niche" 2240:

Schmerk CL, Welander PV, Hamad MA, Bain KL, Bernards MA, Summons RE, Valvano MA (March 2015).

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deposition and persists in the rock record. The diagenetic product of C would be an extended C

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Sáenz JP, Grosser D, Bradley AS, Lagny TJ, Lavrynenko O, Broda M, Simons K (September 2015).

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Liu W, Sakr E, Schaeffer P, Talbot HM, Donisi J, Härtner T, et al. (September 2014).

8: 818: 810: 686: 451: 175: 116: 112: 3046: 2635: 2584: 2433: 2374: 2310: 1655: 1596: 1366: 1251: 940: 923: 646:-fixation. In contrast, 2-α-methylhopane index values are relatively low across similar 3305: 3288: 3261: 3228: 3204: 3169: 3120: 3065: 3030: 2899: 2864: 2803: 2746: 2665: 2604: 2452: 2417: 2393: 2358: 2329: 2294: 2272: 2214: 2189: 2102: 2085: 1951: 1926: 1899: 1874: 1850: 1825: 1757: 1740: 1716: 1691: 1556: 1531: 1504: 1479: 1385: 1350: 1321: 1294: 1270: 1235: 1206: 1181: 1155: 814: 298: 250: 2139: 2061: 2044: 1421: 1087: 353:

engaging the substrate, squalene, shown in gold. The cyclase is depicted as a monomer.

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and can presumably make hopanoids, which have been shown to play diverse roles in the

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Summons, Roger E.; Jahnke, Linda L.; Hope, Janet M.; Logan, Graham A. (August 1999).

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and colleagues following the discovery of the precursor lipids, 2-methylhopanols, in

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bond on the squalene have attacked the hopenyl carbocation to close the E ring, the C

394: 223: 2276: 387:, meaning pairs of the cyclase are embedded in but do not span the plasma membrane. 3378: 3351: 3300: 3256: 3240: 3199: 3181: 3147: 3124: 3104: 3060: 3050: 3011: 2976: 2937: 2894: 2876: 2836: 2779: 2750: 2730: 2695: 2647: 2639: 2608: 2588: 2510: 2484: 2447: 2437: 2388: 2378: 2324: 2314: 2256: 2209: 2201: 2170: 2135: 2097: 2056: 2017: 1982: 1946: 1938: 1894: 1886: 1845: 1837: 1795: 1752: 1711: 1703: 1659: 1610: 1600: 1551: 1543: 1499: 1491: 1452: 1417: 1380: 1370: 1316: 1306: 1265: 1255: 1201: 1193: 1159: 1147: 1083: 1056: 1014: 981: 935: 894: 513: 2925:"N2-fixing cyanobacteria supplied nutrient N for Cretaceous oceanic anoxic events" 2840: 852: 3015: 834: 690: 621: 605:

cultures and mats. The subsequent discovery of 2-α-methylhopanes supposedly from

531: 527: 520: 405: 370:. Alpha helices are shown in blue, loop regions in green, and beta sheets in red. 156: 512:

during deposition, these diagenetic products can still be useful biomarkers, or

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