Phylogenetic Distribution of Fungal Sterols

Abstract

BackgroundErgosterol has been considered the “fungal sterol” for almost 125 years; however, additional sterol data superimposed on a recent molecular phylogeny of kingdom Fungi reveals a different and more complex situation.Methodology/Principal FindingsThe interpretation of sterol distribution data in a modern phylogenetic context indicates that there is a clear trend from cholesterol and other Δ5 sterols in the earliest diverging fungal species to ergosterol in later diverging fungi. There are, however, deviations from this pattern in certain clades. Sterols of the diverse zoosporic and zygosporic forms exhibit structural diversity with cholesterol and 24-ethyl -Δ5 sterols in zoosporic taxa, and 24-methyl sterols in zygosporic fungi. For example, each of the three monophyletic lineages of zygosporic fungi has distinctive major sterols, ergosterol in Mucorales, 22-dihydroergosterol in Dimargaritales, Harpellales, and Kickxellales (DHK clade), and 24-methyl cholesterol in Entomophthorales. Other departures from ergosterol as the dominant sterol include: 24-ethyl cholesterol in Glomeromycota, 24-ethyl cholest-7-enol and 24-ethyl-cholesta-7,24(28)-dienol in rust fungi, brassicasterol in Taphrinales and hypogeous pezizalean species, and cholesterol in Pneumocystis.Conclusions/SignificanceFive dominant end products of sterol biosynthesis (cholesterol, ergosterol, 24-methyl cholesterol, 24-ethyl cholesterol, brassicasterol), and intermediates in the formation of 24-ethyl cholesterol, are major sterols in 175 species of Fungi. Although most fungi in the most speciose clades have ergosterol as a major sterol, sterols are more varied than currently understood, and their distribution supports certain clades of Fungi in current fungal phylogenies. In addition to the intellectual importance of understanding evolution of sterol synthesis in fungi, there is practical importance because certain antifungal drugs (e.g., azoles) target reactions in the synthesis of ergosterol. These findings also invalidate use of ergosterol as an indicator of biomass of certain fungal taxa (e.g., Glomeromycota). Data from this study are available from the Assembling the Fungal Tree of Life (AFTOL) Structural and Biochemical Database: http://aftol.umn.edu.

A Microbial Oasis in the Hypersaline Atacama Subsurface Discovered by a Life Detector Chip: Implications for the Search for Life on Mars

“…The LDChip results confirm that complex polymers (EPS and lipoteichoic acids) were present in the analyzed samples, which, in turn, constitutes direct evidence of viable life or the remains of recently viable life with abundances especially high at *2 m. A strong fluorescent signal was obtained with an anti-steroid antibody in most of the samples below 2 m. We hypothesize that organomineral complexes bearing structurally similar compounds produced either by bacteria or fungi may have been responsible for such a high signal. A likely candidate was ergosterol, a triterpene lipid that forms part of the fungal cell membranes and functions like cholesterol in animal cells (Weete et al, 2010). To verify the authenticity of the antigen-antibody reactions, some samples were heated over a flame in sterile aluminum foil for 10 min in the field laboratory and then analyzed with LDChip300.…”

Distribution and Functions of Sterols and Sphingolipids

“…Both cycloartenol synthase and lanosterol synthase are closely related to each other and to the bacterial squalene-hopene cyclases, which produce the bacterial polycyclic hopenoids without a requirement for molecular oxygen and which are most likely the evolutionary ancestors of the sterol biosynthetic enzymes. Cycloartenol and lanosterol are further metabolized via (de-) methylations and double-bond modifications to give rise to the final sterol products: several C-24 alkylated phytosterols, C 28 campesterol, C 29 sitosterol, and stigmasterol in plants (Benveniste 1986), a single C-24 methylated C 28 ergosterol in most fungi (Weete et al 2010), and the single nonmethylated C 27 cholesterol in animals (Gaylor 2002) (Table 1). Most invertebrates including the important genetic model organisms Drosophila melanogaster and Caenorhabditis elegans have lost the ability to synthesize sterols (Clayton 1964;Kurzchalia and Ward 2003).…”

SREBP-Dependent Triazole Susceptibility in Aspergillus fumigatus Is Mediated through Direct Transcriptional Regulation oferg11A(cyp51A)

“…As ergosterol is the main sterol component of the cell membrane in most ascomycetes (53), and as this synthesis pathway and its resulting product is the target of both the polyene and triazole antifungal drugs, a better understanding of the transcriptional regulatory mechanisms of this pathway is clinically relevant. Importantly, transcriptome profiling of ⌬srbA in A. fumigatus has demonstrated differential regulation of erg3, erg25, and erg24, suggesting that regulation of sterol biosynthesis is also conserved in A. fumigatus (7a, 55).…”