Hopanoids

This group of pentacyclic molecules therefore refers to simple hopenes, hopanols and hopanes, but also to extensively functionalized derivatives such as bacteriohopanepolyols (BHPs) and hopanoids covalently attached to lipid A.

[4] Hopanoids have stable polycyclic structures that are well-preserved in petroleum reservoirs, rocks and sediment, allowing the diagenetic products of these molecules to be interpreted as biomarkers for the presence of specific microbes and potentially for chemical or physical conditions at the time of deposition.

[6][7] About 10% of sequenced bacterial genomes have a putative shc gene encoding a squalene-hopene cyclase and can presumably make hopanoids, which have been shown to play diverse roles in the plasma membrane and may allow some organisms to adapt in extreme environments.

[10] The role of hopanoids in membrane-mediated acid tolerance is further supported by observations of acid-inhibited growth and morphological abnormalities of the plasma membrane in hopanoid-deficient bacteria with mutant squalene-hopene cyclases.

[9] In the actinomycete Frankia, hopanoids in the membranes of vesicles specialized for nitrogen fixation likely restrict the entry of oxygen by making the lipid bilayer more tight and compact.

[17] In Bradyrhizobium, hopanoids chemically bonded to lipid A increase membrane stability and rigidity, enhancing stress tolerance and intracellular survival in Aeschynomene legumes.

[19] In another example of stress tolerance, hopanoids in the aerial hyphae (spore bearing structures) of the prokaryotic soil bacteria Streptomyces are thought to minimize water loss across the membrane to the air.

[22] 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.

[24][25] This enzyme, coded for by the gene shc (also called hpnF in some bacteria), has a double ⍺-barrel fold characteristic of terpenoid biosynthesis[26] and is present in the cell as a monotopic homodimer, meaning pairs of the cyclase are embedded in but do not span the plasma membrane.

[29] For instance, the radical SAM protein HpnH adds an adenosine group to diploptene, forming the extended C35 hopanoid adenosylhopane, which can then be further functionalized by other hpn gene products.

[37] Although hopanoids and sterols are reduced to hopanes and steranes during deposition, these diagenetic products can still be useful biomarkers, or molecular fossils, for studying the coevolution of early life and Earth.

[39] However, molecular clock analyses estimate that the earliest sterols were likely produced around 2.3 Ga ago, around the same time as the Great Oxidation Event, with hopanoid synthesis arising even earlier.

[43] The subsequent discovery of 2-α-methylhopanes supposedly from photosynthetic cyanobacteria in 2.7 Ga old shales from the Pilbara Craton of Western Australia suggested a 400 Ma (million year) gap between the evolution of oxygenic metabolism and the Great Oxidation Event.

[45] Putative cyanobacterial presence on the basis of abundant 2-methylhopanes has been used to explain black shale deposition during Aptian and Cenomanian–Turonian Ocean Anoxic Events (OAEs) and the associated 15N isotopic signatures indicative of N2-fixation.

[19] Research demonstrating that the nitrite-oxidizing bacteria (NOB) Nitrobacter vulgaris increases its production of 2-methylhopanoids 33-fold when supplemented with cobalamin 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 synthesis, respectively.

Active site engineering resulted in loss of the enzyme's ability to form hopanoids, but enabled Brønsted acid catalysis for the stereoselective cyclization of the monoterpenoids geraniol, epoxygeraniol, and citronellal.

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 deposition and persists in the rock record. The diagenetic product of C would be an extended C 35 hopane.
Active site of the squalene-hopene cyclase from Methylococcus capsulatus engaging the substrate, squalene, shown in gold. The cyclase is depicted as a monomer.
Alpha barrel structure of the squalene-hopene cyclase from Methylococcus capsulatus . Alpha helices are shown in blue, loop regions in green, and beta sheets in red.
Structure of a 2-alpha-methylhopane with the carbons of the base hopane structure numbered according to convention. Five rings of carbon, the first four of which are 6-member while the fifth is 5-member, are arranged such that they each share an edge. In the base structure, the rings are singly methylated at carbon numbers 8, 10, 14, and 18, and doubly methylated at carbon number 4. The twenty-first carbon, located in the fifth ring, is bound to the second carbon in an 8 carbon chain. In 2-alpha-methylhopane, the compound is methylated at carbon number 2. This additional methyl group is indicated in red.
Structure of a 2-α-methylhopane with the carbons of the base hopane structure numbered according to convention. The methyl group at the C 2 position is indicated in red.