Sterol Biosynthesis Inhibitors Research Articles

Functional Characterization of the Sterol-Synthesis-Related Gene CgCYP51 in the Poplar Anthracnose-Causing Fungus Colletotrichum gloeosporioides

Poplar is an economically and ecologically valuable tree species. Anthracnose, which severely affects poplar tree growth, is mainly caused by Colletotrichum gloeosporioides. In the infestation cycle of poplar anthracnose, the entry of C. gloeosporioides into the host tissue depends on the formation of an appressorium. The subsequent development of the appressorium determines the pathogenesis of poplar anthracnose and the degree of damage. Previous studies have found that the transcription factor CgSte12 affects appressorium formation and development by regulating the expression of a series of genes, including the sterol-synthesis-related gene CgCYP51, which influences appressorium formation and development. In this study, knockout and functional analyses of CgCYP51 revealed decreases in differentiation, darkening rate, and turgor pressure of appressoria in mutants. Additionally, compared with the wild-type appressorium, mutant appressoria secreted less mucus and exhibited abnormal penetration pore formation, ultimately leading to decreased pathogenicity. Moreover, CgCyp51 affected the sensitivity of C. gloeosporioides to sterol biosynthesis inhibitors. Considered together, the study findings indicate CgCYP51 is a key CgSte12-regulated gene that affects C. gloeosporioides appressorium formation and development. Furthermore, the study data provide new insights into the molecular basis of C. gloeosporioides appressorium formation and development.

Uncovering the Hidden Potential of Phytoene Production by the Fungus Blakeslea trispora.

Phytoene is an uncommon linear carotene within the carotenoid group as it is colorless due to its short chromophore. Recent research constitutes a relatively new area which has emerged from phytoene's importance as a major dietary carotenoid promoting health and appearance. Its resources point to the potential of biotechnological production systems. Our work has been designed to study the efficacy of two colored carotenoid biosynthesis inhibitors, diphenylamine and 2-methyl imidazole, and one sterol biosynthesis inhibitor, terbinafine, to modify the metabolic flux in mated cultures of Blakeslea trispora to achieve maximum phytoene production. Bioprocess kinetics optimized by response surface methodology and monitored by high-performance liquid chromatography revealed maximum phytoene content (5.02 mg/g dry biomass) and yield (203.91 mg/L culture medium) comparable or even higher than those reported for other potent phytoene microbial producers. The in vivo antioxidant activity of phytoene-rich carotenoid extract from fungal cells was also considered and discussed.

Genetic algorithm multiple linear regression and machine learning-driven QSTR modeling for the acute toxicity of sterol biosynthesis inhibitor fungicides

Sterol Biosynthesis Inhibitors (SBIs) are a major class of fungicides used globally. Their widespread application in agriculture raises concerns about potential harm and toxicity to non-target organisms, including humans. To address these concerns, a quantitative structure-toxicity relationship (QSTR) modeling approach has been developed to assess the acute toxicity of 45 different SBIs. The genetic algorithm (GA) was used to identify key molecular descriptors influencing toxicity. These descriptors were then used to build robust QSTR models using multiple linear regression (MLR), support vector regression (SVR), and artificial neural network (ANN) algorithms. The Cross-validation, Y-randomization test, applicability domain methods, and external validation were carried out to evaluate the accuracy and validity of the generated models. The MLR model exhibited satisfactory predictive performance, with an R2 of 0.72. The SVR and ANN models obtained R2 values of 0.7 and 0.8, respectively. ANN model demonstrated superior performance compared to other models, achieving R2cv and R2test values of 0.74 and 0.7, respectively. The models passed both internal and external validation, indicating their robustness. These models offer a valuable tool for risk assessment, enabling the evaluation of potential hazards associated with future applications of SBIs.

Exposure to sublethal levels of insecticide-fungicide mixtures affect reproductive success and population growth rates in the solitary bee Osmia cornuta

In agricultural environments, bees are routinely exposed to combinations of pesticides. For the most part, exposure to these pesticide mixtures does not result in acute lethal effects, but we know very little about potential sublethal effects and their consequences on reproductive success and population dynamics. In this study, we orally exposed newly emerged females of the solitary bee Osmia cornuta to environmentally-relevant levels of acetamiprid (a cyano-substituted neonicotinoid insecticide) singly and in combination with tebuconazole (a sterol-biosynthesis inhibitor (SBI) fungicide). The amount of feeding solution consumed during the exposure phase was lowest in bees exposed to the pesticide mixture. Following exposure, females were individually marked and released into oilseed rape field cages to monitor their nesting performance and assess their reproductive success. The nesting performance and reproductive success of bees exposed to the fungicide or the insecticide alone were similar to those of control bees and resulted in a 1.3–1.7 net population increases. By contrast, bees exposed to the pesticide mixture showed lower establishment, shortened nesting period, and reduced fecundity. Together, these effects led to a 0.5–0.6 population decrease. Female establishment and shortened nesting period were the main population bottlenecks. We found no effects of the pesticide mixture on nest provisioning rate, offspring body weight or sex ratio. Our study shows how sublethal pesticide exposure may affect several components of bee reproductive success and, ultimately, population growth. Our results calls for a rethinking of pollinator risk assessment schemes, which should target not only single compounds but also combinations of compounds likely to co-occur in agricultural environments.

Amoebicidal Effect of COVID Box Molecules against Acanthamoeba: A Study of Cell Death.

Acanthamoeba spp. can cause a sight threatening disease. At present, the current treatments used to treat Acanthamoeba spp. Infections, such as biguanide-based antimicrobials, remain inefficacious, with the appearance of resistant forms and high cytotoxicity to host cells. In this study, an initial screening was conducted against Acanthamoeba castellanii Neff and murine macrophages J774A.1 using alamarBlue™. Among the 160 compounds included in the cited box, 90% exhibited an inhibition of the parasite above 80%, while only 18.75% of the compounds inhibited the parasite with a lethality towards murine macrophage lower than 20%. Based on the amoebicidal activity, the cytotoxicity assay, and availability, Terconazole was chosen for the elucidation of the action mode in two clinical strains, Acanthamoeba culbertsoni and Acanthamoeba castellanii L10. A fluorescence image-based system and proteomic techniques were used to investigate the effect of the present azole on the cytoskeleton network and various programmed cell death features, including chromatin condensation and mitochondria dysfunction. Taking all the results together, we can suggest that Terconazole can induce programmed cell death (PCD) via the inhibition of sterol biosynthesis inhibition.

Structure-Based Optimization of Novel Sterol 24-C-Methyltransferase Inhibitors for the Treatment of Candida albicans Infections.

Interfering with sterol biosynthesis is an important strategy for developing safe and effective antifungal drugs. We previously identified compound H55 as an allosteric inhibitor of the fungal-specific C-24 sterol methyltransferase Erg6 for treating Candida albicans infections. Herein, 62 derivatives of H55 were designed and synthesized based on target-ligand interactions to identify more active candidates. Among them, d28 displayed the most potent antivirulence ability (MHIC50 = 0.25 μg/mL) by targeting Erg6, exhibiting an 8-fold increase in potency compared with H55. Moreover, d28 significantly outperformed H55 in inhibiting cell adhesion and biofilm formation, and exhibited minimal cytotoxicity and negligible potential to induce drug resistance. Of note, the coadministration of d28 and other sterol biosynthesis inhibitors, such as tridemorph or terbinafine, demonstrated a strong synergistic antifungal action in vitro and in vivo in a murine skin infection model. These results support the potential application of d28 in the treatment of C. albicans infections.

Evaluation of the ecological risk of pesticide residues from the European LUCAS Soil monitoring 2018 survey.

The 2018 LUCAS (Land Use and Coverage Area frame Survey) Soil Pesticides survey provides a European Union (EU)-scale assessment of 118 pesticide residues in more than 3473 soil sites. This study responds to the policy need to develop risk-based indicators for pesticides in the environment. Two mixture risk indicators are presented for soil based, respectively, on the lowest and the median of available No Observed Effect Concentration (NOECsoil,min and NOECsoil,50) from publicly available toxicity datasets. Two further indicators were developed based on the corresponding equilibrium concentration in the aqueous phase and aquatic toxicity data, which are available as species sensitivity distributions. Pesticides were quantified in 74.5% of the sites. The mixture risk indicator based on the NOECsoil,min exceeds 1 in 14% of the sites and 0.1 in 23%. The insecticides imidacloprid and chlorpyrifos and the fungicide epoxiconazole are the largest contributors to the overall risk. At each site, one or a few substances drive mixture risk. Modes of actions most likely associated with mixture effects include modulation of acetylcholine metabolism (neonicotinoids and organophosphate substances) and sterol biosynthesis inhibition (triazole fungicides). Several pesticides driving the risk have been phased out since 2018. Following LUCAS surveys will determine the effectiveness of substance-specific risk management and the overall progress toward risk reduction targets established by EU and UN policies. Newly generated data and knowledge will stimulate needed future research on pesticides, soil health, and biodiversity protection. Integr Environ Assess Manag 2024;20:1639-1653. © 2024 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Stimulation of estrogen receptor-alpha by hydroxyanilide fungicide, fenhexamid promotes lipid accumulation in 3 T3-L1 adipocyte

Fenhexamid are fungicides that act against plant pathogens by inhibiting sterol biosynthesis. Nonetheless, it can trigger endocrine disruption and promote breast cancer cell growth. In a recent study, we investigated the mechanism underlying the lipid accumulation induced by fenhexamid hydroxyanilide fungicides in 3 T3-L1 adipocytes. To examine the estrogen receptor alpha (ERα)-agonistic effect, ER transactivation assay using the ERα-HeLa-9903 cell line was applied, and fenhexamid-induced ERα agonist effect was confirmed.Further confirmation that ERα-dependent lipid accumulation occurred was provided by treating 3 T3-L1 adipocytes with Methyl-piperidino-pyrazole hydrate (MPP), an ERα-selective antagonist. Fenhexamid mimicked the actions of ERα agonists and impacted lipid metabolism, and its mechanism involves upregulation of the expression of transcription factors that facilitate adipogenesis and lipogenesis. Additionally, it stimulated the expression of peroxisome proliferator-activated receptor (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα), fatty acid synthase (FAS), and sterol regulatory element-binding protein 1 (SREBP1) and significantly elevated the expression of fatty acid-binding protein 4 (FABP4). In contrast, in combination with an ERα-selective antagonist, fenhexamid suppressed the expression of adipogenic/lipogenic transcription factors.These results suggest that fenhexamid affects the endocrine system and leads to lipid accumulation by interfering with processes influenced by ERα activation.

Sterol Biosynthesis Contributes to Brefeldin-A-Induced Endoplasmic Reticulum Stress Resistance inChlamydomonas reinhardtii.

The endoplasmic reticulum (ER) stress response is an evolutionarily conserved mechanism in most eukaryotes. In this response, sterols in the phospholipid bilayer play a crucial role in controlling membrane fluidity and homeostasis. Despite the significance of both the ER stress response and sterols in maintaining ER homeostasis, their relationship remains poorly explored. Our investigation focused on Chlamydomonas strain CC-4533 and revealed that free sterol biosynthesis increased in response to ER stress, except in mutants of the ER stress sensor Inositol-requiring enzyme 1 (IRE1). Transcript analysis of Chlamydomonas experiencing ER stress unveiled the regulatory role of the IRE1/basic leucine zipper 1 pathway in inducing the expression of ERG5, which encodes C-22 sterol desaturase. Through the isolation of three erg5 mutant alleles, we observed a defect in the synthesis of Chlamydomonas' sterol end products, ergosterol and 7-dehydroporiferasterol. Furthermore, these erg5 mutants also exhibited increased sensitivity to ER stress induced by brefeldin A (BFA, an inhibitor of ER-Golgi trafficking), whereas tunicamycin (an inhibitor of N-glycosylation) and dithiothreitol (an inhibitor of disulfide-bond formation) had no such effect. Intriguingly, the sterol biosynthesis inhibitors fenpropimorph and fenhexamid, which impede steps upstream of the ERG5 enzyme in sterol biosynthesis, rescued BFA hypersensitivity in CC-4533 cells. Collectively, our findings support the conclusion that the accumulation of intermediates in the sterol biosynthetic pathway influences ER stress in a complex manner. This study highlights the significance and complexity of regulating sterol biosynthesis during the ER stress response in microalgae.

Powdery Mildew A Disease of Grapes And The Fungicides Mode of Action: A Review

Powdery mildew caused by Uncinula necator (Schw.) Burr. is one of the widespread fungal diseases of grapes that have caused economic losses through poor fruit set and low yield substantially. To decrease the inoculum potential, a disease management program must be undertaken early in the season which is imperative to reduce late-season disease problems. Because, without early control of the infection of powdery mildew, often lead to severe problem in the late season. Elemental sulfur was the foremost antifungal utilized for the control of powdery mildew which is still in use as an effective and cheap fungicide for vineyards. Sterolbiosynthesis inhibitors (SI), also called SI fungicides, are the latest products to control powdery mildew effectively. For efficient use of fungicides with no or less resistance to the pathogen, it is appropriate to spray fungicides having different mechanisms of action which are specific in function, and for more efficacy, use a mixture of such fungicides that have no harmful impact on plant growth and environment. So, for effective control of powdery mildew, a protective spray of fungicide before bloom and a subsequent spray of systemic fungicides at the time of berry formation ensure healthy and higher grapes yield. This paper reviewed the powdery mildew infection in grapevines and its effect on yield losses with details of fungicides’ mechanism of action and newly developed fungicides having broad spectrum activities.

Sterols and Sphingolipids as New Players in Cell Wall Building and Apical Growth of Nicotiana tabacum L. Pollen Tubes

Pollen tubes are tip-growing cells that create safe routes to convey sperm cells to the embryo sac for double fertilization. Recent studies have purified and biochemically characterized detergent-insoluble membranes from tobacco pollen tubes. These microdomains, called lipid rafts, are rich in sterols and sphingolipids and are involved in cell polarization in organisms evolutionarily distant, such as fungi and mammals. The presence of actin in tobacco pollen tube detergent-insoluble membranes and the preferential distribution of these domains on the apical plasma membrane encouraged us to formulate the intriguing hypothesis that sterols and sphingolipids could be a "trait d'union" between actin dynamics and polarized secretion at the tip. To unravel the role of sterols and sphingolipids in tobacco pollen tube growth, we used squalestatin and myriocin, inhibitors of sterol and sphingolipid biosynthesis, respectively, to determine whether lipid modifications affect actin fringe morphology and dynamics, leading to changes in clear zone organization and cell wall deposition, thus suggesting a role played by these lipids in successful fertilization.

Design, Synthesis, and Evaluation of Novel 4-Chloropyrazole-Based Pyridines as Potent Fungicide Candidates.

A rational molecular design approach was developed in our laboratory to guide the discovery of novel sterol biosynthesis inhibitors. Based on the application of bioactivities of heterocyclic rings and molecular docking targeting the sterol biosynthesis 14α-demethylase, a series of 4-chloropyrazole-based pyridine derivatives were rationally designed, synthesized, and characterized and their fungicidal activities were also evaluated. Bioassay results showed that 7e, 7f, and 7m exhibited commendable, diverse antifungal actions that are comparable to those of the positive controls imazalil and triadimefon. The active compounds' mode of action was further studied by microscopy observations, Q-PCR, and enzyme inhibition assay and discovered that target compounds affect fungal sterol biosynthesis via disturbing RcCYP51 enzyme system. These findings support that their fungicidal mode of action still targets the cytochrome P450-dependent 14α-demethylase as the molecular design did at first. The above results strongly suggest that our rational molecular design protocol is not only practical but also efficient.

Individual and simultaneous treatment with antipsychotic aripiprazole and antidepressant trazodone inhibit sterol biosynthesis in the adult brain

Polypharmacy, or the simultaneous use of multiple drugs to treat a single patient, is a common practice in psychiatry. Unfortunately, data on the health effects of commonly used combinations of medications are very limited. In this study, we therefore investigated the effects and interactions between two commonly prescribed psychotropic medications with sterol inhibiting side effects, trazodone (TRZ), an antidepressant, and aripiprazole (ARI), an antipsychotic. In vitro cell culture experiments revealed that both medications alone disrupted neuronal and astroglial sterol biosynthesis in dose-dependent manners. Furthermore, when ARI and TRZ were combined, exposure resulted in an additive 7-dehydrocholesterol (7-DHC) increase, as well as desmosterol (DES) and cholesterol decreases in both cell types. In adult mice, at baseline, we found that the three investigated sterols showed significant differences in distribution across the eight assessed brain regions. Furthermore, experimental mice treated with ARI or TRZ, or a combination of both medications for 8 days, showed strong sterol disruption across all brain regions. We show ARI or TRZ alone elevated 7-DHC and decreased DES levels in all brain regions, but with regional differences. However, the combined utilization of these two medications for 8 days did not lead to additive changes in sterol disturbances. Based on the complex roles of 7-DHC derived oxysterols, we conclude that individual and potentially simultaneous use of medications with sterol biosynthesis-inhibiting properties might have undesired side effects on the adult brain, with as yet unknown long-term consequences on mental or physical health.

Sterol Metabolism Differentially Contributes to Maintenance and Exit of Quiescence.

Nutrient starvation initiates cell cycle exit and entry into quiescence, a reversible, non-proliferative state characterized by stress tolerance, longevity and large-scale remodeling of subcellular structures. Depending on the nature of the depleted nutrient, yeast cells are assumed to enter heterogeneous quiescent states with unique but mostly unexplored characteristics. Here, we show that storage and consumption of neutral lipids in lipid droplets (LDs) differentially impacts the regulation of quiescence driven by glucose or phosphate starvation. Upon prolonged glucose exhaustion, LDs were degraded in the vacuole via Atg1-dependent lipophagy. In contrast, yeast cells entering quiescence due to phosphate exhaustion massively over-accumulated LDs that clustered at the vacuolar surface but were not engulfed via lipophagy. Excessive LD biogenesis required contact formation between the endoplasmic reticulum and the vacuole at nucleus-vacuole junctions and was accompanied by a shift of the cellular lipid profile from membrane towards storage lipids, driven by a transcriptional upregulation of enzymes generating neutral lipids, in particular sterol esters. Importantly, sterol ester biogenesis was critical for long-term survival of phosphate-exhausted cells and supported rapid quiescence exit upon nutrient replenishment, but was dispensable for survival and regrowth of glucose-exhausted cells. Instead, these cells relied on de novo synthesis of sterols and fatty acids for quiescence exit and regrowth. Phosphate-exhausted cells efficiently mobilized storage lipids to support several rounds of cell division even in presence of inhibitors of fatty acid and sterol biosynthesis. In sum, our results show that neutral lipid biosynthesis and mobilization to support quiescence maintenance and exit is tailored to the respective nutrient scarcity.

Host cholesterol influences the activity of sterol biosynthesis inhibitors in Leishmania amazonensis.

A significant percentage of exogenous cholesterol was found in promastigotes and amastigotes of all studied species of Leishmania, suggesting a biological role for this molecule. Previous studies have shown that promastigotes of Leishmania uptake more low-density lipoprotein (LDL) particles under pharmacological pressure and are more susceptible to ergosterol inhibition in the absence of exogenous sources of cholesterol. This work shows that the host’s LDL is available to intracellular amastigotes and that the absence of exogenous cholesterol enhances the potency of sterol biosynthesis inhibitors in infected macrophages. A complete understanding of cholesterol transport to the parasitophorous vacuole can guide the development of a new drug class to be used in combination with sterol biosynthesis inhibitors for the treatment of leishmaniases.

Mitochondrial dysfunction on Leishmania (Leishmania) amazonensis induced by ketoconazole: insights into drug mode of action

BACKGROUND Leishmania parasites cause leishmaniasis that range from self-limiting cutaneous lesions to more serious forms of the disease. The search for potential drug targets focusing on biochemical and metabolic pathways revealed the sterol biosynthesis inhibitors (SBIs) as a promising approach. In this class of inhibitors is found ketoconazole, a classical inhibitor of 14α-methysterol 14-demethylase.OBJECTIVE The present study aimed to better understand the biological response of Leishmania (Leishmania) amazonensis promastigotes at the cellular level after ketoconazole treatment.METHODS Herein, techniques, such as fluorimetry, flow cytometry, fluorescence microscopy, electron and scanning microscopy were used to investigate the cellular structures and to identify organelles affected by ketoconazole treatment.FINDINGS The study demonstrated, for the first time, the effect of ketoconazole on mitochondrion functioning and its probable relationship to cell cycle and death on L. (L.) amazonensis promastigotes (IFLA/BR/67/PH8 strain).MAIN CONCLUSIONS Ketoconazole-induced mitochondrial damages led to hyperpolarisation of this single organelle and autophagic vacuoles formation, as a parasite survival strategy. These damages did not reflect directly on the parasite cell cycle, but drove the parasites to death, making them susceptible to ketoconazole treatment in in vitro models.

Antibacterial Effect of Some Eukaryotic Sterol Biosynthesis Inhibitors.

Isoprenoids and their derivatives are building blocks for the synthesis of biomolecules with important biological functions such as cholesterol in eukaryotes and lipid carrier undecaprenol, which is involved in cell wall biosynthesis in bacteria. With the global threat of multidrug-resistant bacteria, there is a need for finding new metabolic targets for killing bacteria. In the present study, we examined the impact of eukaryotic sterol biosynthesis inhibitors on the growth of four pathogenic bacteria. Antibacterial effect of HMG CoA reductase inhibitor (simvastatin), farnesyl pyrophosphate synthase inhibitor (alendronate), squalene epoxidase inhibitor (terbinafine), and lanosterol demethylase inhibitor (ketoconazole) were studied against four pathogenic bacteria: two gram-positive bacteria, Staphylococcus aureus and Enterococcus faecalis and two gram-negative bacteria, Escherichia coli and Pseudomonas aeruginosa. Broth microdilution method was used for assessing the antibacterial susceptibility of the components using 96 well plats. MIC and MBC were determined visibly. MIC of Ketoconazole for Staphylococcus aureus and Enterococcus faecalis were 0.166 and 1 mg/mL, respectively. Terbinafine had a weak inhibitory effect on Staphylococcus aureus (MIC: 8 mg/mL). Ketoconazole and terbinafine had no inhibitory effect on gram-negative bacteria. MBC of Simvastatin for both Staphylococcus aureus and Enterococcus faecalis was 0.5 mg/mL and of Alendronate for Pseudomonas aeruginosa was 6.6 mg/mL. Our results show that farnesyl pyrophosphate synthase and class II HMG-CoA reductases inhibitors (ketoconazole and simvastatin) have reasonable antibacterial activity against gram-positive bacteria. These two enzymes provide suitable targets for designing new antibiotics based on modifying the chemical structure of currently used drugs to obtain maximum activity.

Relaxed Substrate Requirements of Sterol 14α-Demethylase from Naegleria fowleri Are Accompanied by Resistance to Inhibition.

Naegleria fowleri is the protozoan pathogen that causes primary amoebic meningoencephalitis (PAM), with the death rate exceeding 97%. The amoeba makes sterols and can be targeted by sterol biosynthesis inhibitors. Here, we characterized N. fowleri sterol 14-demethylase, including catalytic properties and inhibition by clinical antifungal drugs and experimental substituted azoles with favorable pharmacokinetics and low toxicity. None of them inhibited the enzyme stoichiometrically. The highest potencies were displayed by posaconazole (IC50 = 0.69 μM) and two of our compounds (IC50 = 1.3 and 0.35 μM). Because both these compounds penetrate the brain with concentrations reaching minimal inhibitory concentration (MIC) values in an N. fowleri cellular assay, we report them as potential drug candidates for PAM. The 2.1 Å crystal structure, in complex with the strongest inhibitor, provides an explanation connecting the enzyme weaker substrate specificity with lower sensitivity to inhibition. It also provides insight into the enzyme/ligand molecular recognition process and suggests directions for the design of more potent inhibitors.

Functions of phytosterols in seed development of upland cotton (Gossypium hirsutum L.)

Cotton seeds are important for the yield of fiber, oil, and protein. Previous studies have shown that phytosterols play important roles in fiber growth. However, the functions of phytosterols in cotton seed development remain to be elucidated. In this study, we detected the phytosterol content of cotton seeds at various developmental stages by gas chromatography–mass spectrometry (GC–MS). We found that the contents of sitosterol and campesterol were higher in the stages from 5 to 25 days post-anthesis (DPA) and decreased rapidly after 25 DPA. Moreover, the ratio of campesterol to sitosterol was low before 15 DPA and high at 20 and 25 DPA. During the early developmental stages of cotton seeds, sitosterol and campesterol are the predominant phytosterols, and the sitosterol content is much higher than that of campesterol. In addition, we found that most phytosterol biosynthetic genes were highly expressed in 10-DPA and/or 20-DPA seeds by qRT-PCR, which was consistent with the phytosterol content in cotton seeds. When the cotton bud was treated with the sterol biosynthesis inhibitors tridemorph and fenpropimorph, the growth of cotton seeds was retarded. Moreover, overexpression of the phytosterol biosynthetic gene GhSMT2−1 significantly increased the size and weight of cotton seeds. These results indicate that phytosterols indeed participate in the regulation of cotton seed development.

The mysterious route of sterols in oomycetes.

Sterols are a class of lipids with essential roles in sustaining the domain structure of cell membranes and regulating biological processes [1]. Human health is affected by high cholesterol levels [2]; drugs preventing this are widely used. Also striking is the high demand for compounds classified as sterol biosynthesis inhibitors (SBIs), either as medicine to control fungal infections or as agrochemicals to combat fungal plant diseases [3,4]. Despite the essential role of sterols in cell functioning in eukaryotes, several organisms, including nematodes, insects, and plasmodia, are not able to synthesize sterols themselves. To sustain normal development, these sterol auxotrophs may have to acquire exogenous sterols from their food or environment [5,6].