Abstract
Metabolomics has become a powerful tool in chemical biology. Profiling the human sterolome has resulted in the discovery of noncanonical sterols, including oxysterols and meiosis-activating sterols. They are important to immune responses and development, and have been reviewed extensively. The triterpenoid metabolite fusidic acid has developed clinical relevance, and many steroidal metabolites from microbial sources possess varying bioactivities. Beyond the prospect of pharmacognostical agents, the profiling of minor metabolites can provide insight into an organism’s biosynthesis and phylogeny, as well as inform drug discovery about infectious diseases. This review aims to highlight recent discoveries from detailed sterolomic profiling in microorganisms and their phylogenic and pharmacological implications.
Highlights
Sterols, like cholesterol 1, ergosterol 2, and sitosterol 3, as well as secondary metabolites, are amphipathic lipids that contain a 1,2-cyclopentanoperhydrophenanthrene ring nucleus (Figure 1).Sterols are ubiquitous molecules found in all eukaryotic life, serving a multitude of crucial biological functions [1]
While sterol biosynthesis may predate eukaryotes [6], it is often hypothesized that aside from the protomitochondrial lineage, most bacteria have gained these genes via lateral gene transfer [3,4]
The algal pathway was further corroborated by characterization of recombinant C. reinhardtii 24wild-type, mutant, and inhibitor-treated cultures revealed an additional 21 sterols beyond cycloartenol, sterol methyltransferase (SMT), found to catalyze the methylation of C24 by introduction of C28 and the methylation of C28 ergosterol, and 7-dehydroporiferasterol 33 [45] (Figure 3)
Summary
Like cholesterol 1, ergosterol 2, and sitosterol 3, as well as secondary metabolites, are amphipathic lipids that contain a 1,2-cyclopentanoperhydrophenanthrene ring nucleus (Figure 1). The end product of ∆5 sterols such as cholesterol 1 and ergosterol 2 (Figure 1a) contribute to cell membrane fluidity in their bulk insert role in mammals and fungi, respectively [1,7]. Designated α and β to reflect the C24 stereochemistries of sitosterol and ergosterol, respectively, as Carbon numbering is provided on 1–4, and stereochemistries at C8, C9, C14, and C16 on structure drawn above. Small molecule ligands for ergosterol biosynthetic enzymes in fungi have long been clinically and agriculturally relevant [23,24,25]. Understanding sterol biosynthesis in non-fungal microbes may provide new insights for insights for treating infections by eukaryotic pathogens.
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