An essential fungal growth factor derived from ergosterol: A new end product of sterol biosynthesis in fungi?

Parks, Leo W.; Rodriguez, Russell J.; Low, Christopher

doi:10.1007/bf02534308

Cited by 21 publications

(10 citation statements)

References 10 publications

(3 reference statements)

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“…This growth inhibition has been reported before (12) and is currently being investigated. A previous report described a water-soluble compound isolated from wild-type S. cerevisiae that allowed sparking on cholestanol (18). This sparking ergosterol replacement factor has the same properties of the heme intermediate ALA, which was shown to spark growth at very low concentrations.…”

Section: Discussionmentioning

confidence: 99%

Structural discrimination in the sparking function of sterols in the yeast Saccharomyces cerevisiae

1989

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A Saccharomyces cerevisiae sterol auxotroph, SPK14 (a hem] erg6 erg7 ura), was constructed to test the ability of selected C-5,6 unsaturated sterols at growth-limiting concentrations to spark growth on bulk cholestanol. The native sterol, ergosterol, initiated growth faster and allowed a greater cell yield than did other sterols selectively altered in one or more features of the sterol. Although the C-5,6 unsaturation is required for the sparking function, the presence of the C-22 unsaturation was found to facilitate sparking far better than did the C-7 unsaturation, whereas the C-24 methyl was the least important group. The addition of 8-aminolevulinic acid to the medium allowed the sparking of FY3 (heml erg7 ura) on bulk cholestanol due to the derepression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase and the production of endogenous ergosterol. The optimal concentration of 8-aminolevulinic acid to spark growth was 800 ng/ml, whereas higher concentrations caused a growth inhibition. The growth yield of FY3 reached a plateau maximum at about 5 ,ug/ml when the bulk cholestanol was varied in the presence of 10 ng of sparking ergosterol per ml.Evidence for differential utilization of sterols has been described in insects (3) and bacteria (5,6,17). Because of its ease of growth and facile genetic manipulations, Saccharomyces cerevisiae has been particularly valuable in studying the diverse functions of sterols. Using the sterol auxotrophs RD5-R and FY3, we demonstrated that the sterol requirement for growth could be fulfilled by cholestanol only when a very small concentration of ergosterol (10 ng/ml) was also present in the medium (23,25,26). We have systematically varied the combinations of sterols that were provided to the auxotrophs, and we proposed multiple roles for sterols in this organism under aerobic conditions. We have designated the cellular requirement that could be satisfied by cholestanol as the bulk function, and the high specificity function fulfilled by microamounts of ergosterol has been termed the sparking function. By feeding different sterols and stanols to RD5-R and FY3, we showed that most sterols and stanols could satisfy the bulk requirement. However, only those sterol derivatives that have a C-5,6 unsaturation or are capable of being desaturated at C-5 fulfill the sparking function (25).Other studies with S. cerevisiae have shown growth preferences for different sterols, depending on the cultural conditions. The sterol auxotroph GL7, grown on limiting amounts of ergosterol, has higher growth rates and yields in media additionally supplemented with cholesterol when compared with growth of the organism on either sterol alone (21). The necessity of the 24 P-methyl group on the sterol was proposed for S. cerevisiae when the wild-type organism is grown under anaerobic conditions in the presence of the synthetic sterol inhibitor 2, 3-iminosqualene (19, 20).Numerous sterols at nonlimiting concentrations (5 ,ug/ml or greater) appear to satisfy the sterol requirement in the presence (22,26) o...

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Section: Discussionmentioning

confidence: 99%

Structural discrimination in the sparking function of sterols in the yeast Saccharomyces cerevisiae

1989

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“…James et al (22) described AmB-resistant isolates of Ustilago maydis that exhibited reduced rates of growth and contained no ergosterol. Actually, ergosterol deficiency was thought to be the main cause of fungal growth delay (26,34). However, the reduced growth rate of strain UTS 1002 appears to be unrelated to ergosterol content because the mutant contained as much ergosterol as the wild-type strain.…”

Section: Discussionmentioning

confidence: 99%

Alteration of Cell Wall Composition Leads to Amphotericin B Resistance in Aspergillus flavus

Seo

Akiyoshi

Ohnishi

1999

Microbiology and Immunology

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An amphotericin B (AmB)‐resistant mutant was isolated from a wild‐type AmB‐susceptible strain of Aspergillus flavus by serial transfer of conidia on agar plates containing stepwise increased concentrations of AmB up to 100 μtg ml−1. The acquired resistance of my celia was specific for polyene‐antibiotics AmB, nystatin and trichomycin. Spheroplasts derived from the resistant mycelia were as susceptible to AmB as the wild‐type. Chemical analysis of the cell wall revealed that levels of alkali‐soluble and ‐insoluble glucans were significantly higher in the resistant mycelia as compared to those in the wild‐type. When resistant mycelia were treated with SDS, they adsorbed as much AmB as wild‐type mycelia. These results suggest that alterations in the cell wall components of mycelia, especially 1,3‐α‐glucan and protein complex in the outermost wall layer, lead to AmB resistance in A. flavus.

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“…This study clearly indicates that cholesterol meets the requirements of yeasts less effectively than ergosterol and furthermore suggests that the sterol molecule can function as a metabolic signal. Parks et al (1986) using that yeast auxotroph RD5-R grown on the saturated sterol, cholestanol, proved again the yeast has a specific growth requirement for a C-5,6-unsaturated sterol. Indeed, this yeast appeared to have a threshold concentration of 1.2 nM (476 ng/l) ergosterol.…”

Section: Studies Using Sterol Auxotrophsmentioning

confidence: 94%

Importance and Role of Sterols in Fungal Membranes

Bossche

1990

Biochemistry of Cell Walls and Membranes in Fungi

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An essential fungal growth factor derived from ergosterol: A new end product of sterol biosynthesis in fungi?

Cited by 21 publications

References 10 publications

Structural discrimination in the sparking function of sterols in the yeast Saccharomyces cerevisiae

Structural discrimination in the sparking function of sterols in the yeast Saccharomyces cerevisiae

Alteration of Cell Wall Composition Leads to Amphotericin B Resistance in Aspergillus flavus

Importance and Role of Sterols in Fungal Membranes

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