Steroids, triterpenoids and molecular oxygen

Abstract

There is a close connection between modern-day biosynthesis of particular triterpenoid biomarkers and presence of molecular oxygen in the environment. Thus, the detection of steroid and triterpenoid hydrocarbons far back in Earth history has been used to infer the antiquity of oxygenic photosynthesis. This prompts the question: were these compounds produced similarly in the past? In this paper, we address this question with a review of the current state of knowledge surrounding the oxygen requirement for steroid biosynthesis and phylogenetic patterns in the distribution of steroid and triterpenoid biosynthetic pathways.The hopanoid and steroid biosynthetic pathways are very highly conserved within the bacterial and eukaryotic domains, respectively. Bacteriohopanepolyols are produced by a wide range of bacteria, and are methylated in significant abundance at the C2 position by oxygen-producing cyanobacteria. On the other hand, sterol biosynthesis is sparsely distributed in distantly related bacterial taxa and the pathways do not produce the wide range of products that characterize eukaryotes. In particular, evidence for sterol biosynthesis by cyanobacteria appears flawed. Our experiments show that cyanobacterial cultures are easily contaminated by sterol-producing rust fungi, which can be eliminated by treatment with cycloheximide affording sterol-free samples.Sterols are ubiquitous features of eukaryotic membranes, and it appears likely that the initial steps in sterol biosynthesis were present in their modern form in the last common ancestor of eukaryotes. Eleven molecules of O 2 are required by four enzymes to produce one molecule of cholesterol. Thermodynamic arguments, optimization of function and parsimony all indicate that an ancestral anaerobic pathway is highly unlikely.The known geological record of molecular fossils, especially steranes and triterpanes, is notable for the limited number of structural motifs that have been observed. With a few exceptions, the carbon skeletons are the same as those found in the lipids of extant organisms and no demonstrably extinct structures have been reported. Furthermore, their patterns of occurrence over billion year time-scales correlate strongly with environments of deposition. Accordingly, biomarkers are excellent indicators of environmental conditions even though the taxonomic affinities of all biomarkers cannot be precisely specified. Biomarkers are ultimately tied to biochemicals with very specific functional properties, and interpretations of the biomarker record will benefit from increased understanding of the biological roles of geologically durable molecules.

On the Age of Eukaryotes: Evaluating Evidence from Fossils and Molecular Clocks

“…A bacterial origin of these biomarkers cannot be excluded as some bacteria make sterols. However, these differ from many that are characteristic of specific eukaryotes (Summons et al 2006;Desmond and Gribaldo 2009). In general, biomarkers need to be considered carefully as contamination is difficult to rule out, and their specificity to one lineage cannot be guaranteed, especially for microbes in which lateral gene transfer is prevalent.…”

Distribution of microbial terpenoid lipid cyclases in the global ocean metagenome

“…Bioinformatics approaches have been used previously to identify terpenoid cyclase genes both in pure cultures (Perzl et al, 1997;Tippelt et al, 1998;Bode et al, 2003;Pearson et al, 2003) as well as in environmental samples . SHCs can be identified readily based on their numerous conserved amino acids (AAs; Hoshino and Sato, 2002;Summons et al, 2006;Fischer and Pearson, 2007). Specific functional motifs (Feil et al, 1996;Wendt et al, 2000) and analysis of secondary structures (Wendt et al, 1997;SchulzGasch and Stahl, 2003) show that the two classes can be distinguished by sequence differences alone.…”

Microaerobic steroid biosynthesis and the molecular fossil record of Archean life

“…These postcyclization modifications involve the chemically challenging activation of unreactive C-H bonds, in which O 2 plays an important role (35). Furthermore, these principal steps in steroid biosynthesis are conserved across some of the deepest phylogenetic divisions in the eukaryotic domain, suggesting that a version of the O 2 -dependent pathway was present in the last common ancestral lineage of all extant eukaryotes (34,36). Although a hypothetical anaerobic route to steroids has been discussed (37), there is no evidence that such a pathway exists today or did so in the past, and operation of the aerobic steroid biosynthesis pathway remains the most plausible explanation for the presence of fossil steranes in the geologic record (34).…”

“…The first O 2 -dependent step is also the first committed step in steroid synthesis: the epoxidation of the linear isoprenoid squalene to produce 2,3-oxidosqualene. The enzyme that cyclizes oxidosqualene to form the characteristic steroidal 6,6,6,5-ring structure cannot act on squalene, but requires squalene (3S) 2,3-epoxide (33,34).…”