⍺-barrel fold characteristic of terpenoid biosynthesis 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. In vitro, this enzyme exhibits promiscuous substrate specificity, also cyclizing 2,3-oxidosqualene. Aromatic residues in the active site form several unfavorable carbocations on the substrate which are quenched by a rapid polycyclization. In the last substep of the cyclization reaction, after electrons comprising the terminal alkene bond on the squalene have attacked the hopenyl carbocation to close the E ring, the C22 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. Functionalization After cyclization, hopanoids are frequently modified by hopanoid biosynthesis enzymes encoded by genes in the same operon as shc, hpn. 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. HpnG catalyzes the removal of adenine 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 glycosyltransferase 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 cyclitol ether. Importantly, C30 and C35 hopanoids alike may be methylated at C2 and C3 positions by the radical SAM methyltransferases HpnP and HpnR, respectively. These two methylations are particularly geostable compared to side-chain modifications and have entertained geobiologists for decades. In a biosynthetic pathway exclusive to some bacteria, the enzyme tetrahymanol synthase catalyzes the conversion of the hopanoid diploptene to the pentacyclic triterpenoid tetrahymanol. In eukaryotes like Tetrahymena, tetrahymanol is instead synthesized directly from squalene by a cyclase with no homology to the bacterial tetrahymanol synthase. In paleobiology 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 1018 gram (1012 ton) in 1992. Biomolecules like DNA and proteins are degraded during diagenesis, but polycyclic lipids persist in the environment over geologic timescales due