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Biomolecules
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Sterol Biosynthesis and Function in Organisms
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Sterol Biosynthesis and Function in Organisms

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: 20 January 2025 | Viewed by 7587

Special Issue Editor

Dr. Hubert Schaller

E-Mail Website
Guest Editor
Institut de Biologie Moléculaire des Plantes, CNRS, Université de Strasbourg, 67084 Strasbourg, France
Interests: phytosterol; isoprenoids; biosynthesis; homeostasis; holobionts

Special Issue Information

Dear Colleagues,

I am pleased to invite you to consider contributing to a Special Issue on sterols entitled “Sterol Biosynthesis and Function in Organisms”.

Sterols are mandatory components of cellular life in eukaryotes. The astonishing variations of the sterolome and the sterol biosynthetic and genetic machinery in organisms are unveiled as genomes are sequenced and functionally analyzed. New enzymes are revealed besides the so-called canonical mevalonate-isoprenoid sterol pathways described in a few models. Sterol-autotroph as well as sterol-auxotroph organisms carve their sterol components for dedicated functions that may differ in the many different eukaryotic lineages. The complexity of the evolutionary history of sterol pathways is not restricted to the latter since a few bacterial phyla contain species that produce sterols.

In this Special Issue, sterol biosynthesis, metabolism and genetic regulation, and structural and biological functions of sterols and sterol conjugates, will be explored in an organismal perspective. Relevant chemical and biochemical tools are part of the strategies to address sterol functions in various cellular processes of crucial importance.

In this Special Issue, original research articles and reviews are welcome. Research areas may include (but not limited to) the following:

  • Plants, algae, photosynthetic organisms;
  • Fungi, unicellular eukaryotes;
  • Invertebrates;
  • Sterol auxotrophs;
  • Interactions, symbiosis;
  • Sterol homeostasis;
  • Bacterial sterols;
  • Enzymes;
  • Inhibitors;
  • Biomarkers.

Dr. Hubert Schaller
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • sterol
  • biosynthesis
  • function
  • organisms

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Published Papers (6 papers)

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Research

Jump to: Review

18 pages, 12170 KiB  
Article
Characterization of Subcellular Dynamics of Sterol Methyltransferases Clarifies Defective Cell Division in smt2 smt3, a C-24 Ethyl Sterol-Deficient Mutant of Arabidopsis
by Daisaku Ohta, Ayaka Fuwa, Yuka Yamaroku, Kazuki Isobe, Masatoshi Nakamoto, Atsushi Okazawa, Takumi Ogawa, Kazuo Ebine, Takashi Ueda, Pierre Mercier and Hubert Schaller
Biomolecules 2024, 14(7), 868; https://doi.org/10.3390/biom14070868 - 19 Jul 2024
Viewed by 908
Abstract
An Arabidopsis sterol mutant, smt2 smt3, defective in sterolmethyltransferase2 (SMT2), exhibits severe growth abnormalities. The loss of C-24 ethyl sterols, maintaining the biosynthesis of C-24 methyl sterols and brassinosteroids, suggests specific roles of C-24 ethyl sterols. We characterized the subcellular localizations of [...] Read more.
An Arabidopsis sterol mutant, smt2 smt3, defective in sterolmethyltransferase2 (SMT2), exhibits severe growth abnormalities. The loss of C-24 ethyl sterols, maintaining the biosynthesis of C-24 methyl sterols and brassinosteroids, suggests specific roles of C-24 ethyl sterols. We characterized the subcellular localizations of fluorescent protein-fused sterol biosynthetic enzymes, such as SMT2-GFP, and found these enzymes in the endoplasmic reticulum during interphase and identified their movement to the division plane during cytokinesis. The mobilization of endoplasmic reticulum-localized SMT2-GFP was independent of the polarized transport of cytokinetic vesicles to the division plane. In smt2 smt3, SMT2-GFP moved to the abnormal division plane, and unclear cell plate ends were surrounded by hazy structures from SMT2-GFP fluorescent signals and unincorporated cellulose debris. Unusual cortical microtubule organization and impaired cytoskeletal function accompanied the failure to determine the cortical division site and division plane formation. These results indicated that both endoplasmic reticulum membrane remodeling and cytokinetic vesicle transport during cytokinesis were impaired, resulting in the defects of cell wall generation. The cell wall integrity was compromised in the daughter cells, preventing the correct determination of the subsequent cell division site. We discuss the possible roles of C-24 ethyl sterols in the interaction between the cytoskeletal network and the plasma membrane. Full article
(This article belongs to the Special Issue Sterol Biosynthesis and Function in Organisms)
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24 pages, 2027 KiB  
Article
Identification of Potential New Genes Related to the SREBP Pathway in Xanthophyllomyces dendrorhous
by Maximiliano Venegas, Alejandro Durán, Sebastián Campusano, Salvador Barahona, Dionisia Sepúlveda, Marcelo Baeza, Víctor Cifuentes and Jennifer Alcaíno
Biomolecules 2024, 14(7), 778; https://doi.org/10.3390/biom14070778 - 29 Jun 2024
Viewed by 926
Abstract
The sterol regulatory element-binding protein (SREBP) pathway is an integral cellular mechanism that regulates lipid homeostasis, in which transcriptional activator SREBPs regulate the expression of various genes. In the carotenogenic yeast Xanthophyllomyces dendrorhous, Sre1 (the yeast SREBP homolog) regulates lipid biosynthesis and [...] Read more.
The sterol regulatory element-binding protein (SREBP) pathway is an integral cellular mechanism that regulates lipid homeostasis, in which transcriptional activator SREBPs regulate the expression of various genes. In the carotenogenic yeast Xanthophyllomyces dendrorhous, Sre1 (the yeast SREBP homolog) regulates lipid biosynthesis and carotenogenesis, among other processes. Despite the characterization of several components of the SREBP pathway across various eukaryotes, the specific elements of this pathway in X. dendrorhous remain largely unknown. This study aimed to explore the potential regulatory mechanisms of the SREBP pathway in X. dendrorhous using the strain CBS.cyp61- as a model, which is known to have Sre1 in its active state under standard culture conditions, resulting in a carotenoid-overproducing phenotype. This strain was subjected to random mutagenesis with N-methyl-N’-nitro-N-nitrosoguanidine (NTG), followed by a screening methodology that focused on identifying mutants with altered Sre1 activation phenotypes. Single-nucleotide polymorphism (SNP) analysis of 20 selected mutants detected 5439 single-nucleotide variants (SNVs), narrowing them down to 1327 SNPs of interest after a series of filters. Classification based on SNP impact identified 116 candidate genes, including 49 genes with high impact and 68 genes with deleterious moderate-impact mutations. BLAST, InterProScan, and gene ontology enrichment analyses highlighted 25 genes as potential participants in regulating Sre1 in X. dendrorhous. The key findings of this study include the identification of genes potentially encoding proteins involved in protein import/export to the nucleus, sterol biosynthesis, the ubiquitin–proteasome system, protein regulatory activities such as deacetylases, a subset of kinases and proteases, as well as transcription factors that could be influential in SREBP regulation. These findings are expected to significantly contribute to the current understanding of the intricate regulation of the transcription factor Sre1 in X. dendrorhous, providing valuable groundwork for future research and potential biotechnological applications. Full article
(This article belongs to the Special Issue Sterol Biosynthesis and Function in Organisms)
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12 pages, 842 KiB  
Article
Synthesis of a Side Chain Alkyne Analogue of Sitosterol as a Chemical Probe for Imaging in Plant Cells
by Miriam Hollweck, David Jordan and Franz Bracher
Biomolecules 2024, 14(5), 542; https://doi.org/10.3390/biom14050542 - 30 Apr 2024
Cited by 1 | Viewed by 1152
Abstract
Clickable chemical tools are essential for studying the localization and role of biomolecules in living cells. For this purpose, alkyne-based close analogs of the respective biomolecules are of outstanding interest. Here, in the field of phytosterols, we present the first alkyne derivative of [...] Read more.
Clickable chemical tools are essential for studying the localization and role of biomolecules in living cells. For this purpose, alkyne-based close analogs of the respective biomolecules are of outstanding interest. Here, in the field of phytosterols, we present the first alkyne derivative of sitosterol, which fulfills the crucial requirements for such a chemical tool as follows: very similar in size and lipophilicity to the plant phytosterols, and correct absolute configuration at C-24. The alkyne sitosterol FB-DJ-1 was synthesized, starting from stigmasterol, which comprised nine steps, utilizing a novel alkyne activation method, a Johnson–Claisen rearrangement for the stereoselective construction of a branched sterol side chain, and a Bestmann–Ohira reaction for the generation of the alkyne moiety. Full article
(This article belongs to the Special Issue Sterol Biosynthesis and Function in Organisms)
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Review

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19 pages, 1654 KiB  
Review
Loss of Sterol Biosynthesis in Economically Important Plant Pests and Pathogens: A Review of a Potential Target for Pest Control
by Paul Dahlin and Andrea Caroline Ruthes
Biomolecules 2024, 14(11), 1435; https://doi.org/10.3390/biom14111435 - 11 Nov 2024
Viewed by 406
Abstract
Sterol biosynthesis is a crucial metabolic pathway in plants and various plant pathogens. Their vital physiological role in multicellular organisms and their effects on growth and reproduction underline their importance as membrane compounds, hormone precursors, and signaling molecules. Insects, nematodes, and oomycetes of [...] Read more.
Sterol biosynthesis is a crucial metabolic pathway in plants and various plant pathogens. Their vital physiological role in multicellular organisms and their effects on growth and reproduction underline their importance as membrane compounds, hormone precursors, and signaling molecules. Insects, nematodes, and oomycetes of the Peronosporales group, which harbor important agricultural pests and pathogens, have lost the ability to synthesize their own sterols. These organisms rely on the acquisition of sterols from their host and are dependent on the sterol composition of the host. It is thought that sterol-synthesizing enzymes were lost during co-evolution with the hosts, which provided the organisms with sufficient amounts of the required sterols. To meet the essential requirements of these organisms, some sterol auxotrophs retained a few remaining sterol-modifying enzymes. Several molecular and biochemical investigations have suggested promising avenues for pest and pathogen control by targeting host sterol composition, sterol uptake, or sterol modification in organisms that have lost the ability to biosynthesize sterol de novo. This review examines the loss of sterol biosynthesis de novo in insects, nematodes, and oomycetes with the aim of investigating the sterol metabolic constraints and sterol acquisition of these organisms. This will shed light on its potential as a control target for the management of sterol-dependent organisms in a comprehensive agronomic approach. Full article
(This article belongs to the Special Issue Sterol Biosynthesis and Function in Organisms)
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13 pages, 2575 KiB  
Review
Bottlenecks in the Investigation of Retinal Sterol Homeostasis
by Sriganesh Ramachandra Rao and Steven J. Fliesler
Biomolecules 2024, 14(3), 341; https://doi.org/10.3390/biom14030341 - 12 Mar 2024
Cited by 2 | Viewed by 1356
Abstract
Sterol homeostasis in mammalian cells and tissues involves balancing three fundamental processes: de novo sterol biosynthesis; sterol import (e.g., from blood-borne lipoproteins); and sterol export. In complex tissues, composed of multiple different cell types (such as the retina), import and export also may [...] Read more.
Sterol homeostasis in mammalian cells and tissues involves balancing three fundamental processes: de novo sterol biosynthesis; sterol import (e.g., from blood-borne lipoproteins); and sterol export. In complex tissues, composed of multiple different cell types (such as the retina), import and export also may involve intratissue, intercellular sterol exchange. Disruption of any of these processes can result in pathologies that impact the normal structure and function of the retina. Here, we provide a brief overview of what is known currently about sterol homeostasis in the vertebrate retina and offer a proposed path for future experimental work to further our understanding of these processes, with relevance to the development of novel therapeutic interventions for human diseases involving defective sterol homeostasis. Full article
(This article belongs to the Special Issue Sterol Biosynthesis and Function in Organisms)
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34 pages, 8249 KiB  
Review
Druggable Sterol Metabolizing Enzymes in Infectious Diseases: Cell Targets to Therapeutic Leads
by W. David Nes, Minu Chaudhuri and David J. Leaver
Biomolecules 2024, 14(3), 249; https://doi.org/10.3390/biom14030249 - 20 Feb 2024
Viewed by 1831
Abstract
Sterol biosynthesis via the mevalonate-isoprenoid pathway produces ergosterol (24β-methyl cholesta-5,7-dienol) necessary for growth in a wide-range of eukaryotic pathogenic organisms in eukaryotes, including the fungi, trypanosomes and amoebae, while their animal hosts synthesize a structurally less complicated product—cholesterol (cholest-5-enol). Because phyla-specific differences in [...] Read more.
Sterol biosynthesis via the mevalonate-isoprenoid pathway produces ergosterol (24β-methyl cholesta-5,7-dienol) necessary for growth in a wide-range of eukaryotic pathogenic organisms in eukaryotes, including the fungi, trypanosomes and amoebae, while their animal hosts synthesize a structurally less complicated product—cholesterol (cholest-5-enol). Because phyla-specific differences in sterol metabolizing enzyme architecture governs the binding and reaction properties of substrates and inhibitors while the order of sterol metabolizing enzymes involved in steroidogenesis determine the positioning of crucial chokepoint enzymes in the biosynthetic pathway, the selectivity and effectiveness of rationally designed ergosterol biosynthesis inhibitors toward ergosterol-dependent infectious diseases varies greatly. Recent research has revealed an evolving toolbox of mechanistically distinct tight-binding inhibitors against two crucial methylation-demethylation biocatalysts—the C24 sterol methyl transferase (absent from humans) and the C14-sterol demethylase (present generally in humans and their eukaryotic pathogens). Importantly for rational drug design and development, the activities of these enzymes can be selectively blocked in ergosterol biosynthesis causing loss of ergosterol and cell killing without harm to the host organism. Here, we examine recent advances in our understanding of sterol biosynthesis and the reaction differences in catalysis for sterol methylation-demethylation enzymes across kingdoms. In addition, the novelties and nuances of structure-guided or mechanism-based approaches based on crystallographic mappings and substrate specificities of the relevant enzyme are contrasted to conventional phenotypic screening of small molecules as an approach to develop new and more effective pharmacological leads. Full article
(This article belongs to the Special Issue Sterol Biosynthesis and Function in Organisms)
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