N‐Fatty Acylation of Hydrolyzed Fumonisin B1, But Not of Intact Fumonisin B1, Strongly Enhances In Vitro Mammalian Toxicity

This article describes clinical, etiologic and pathologic diagnosis of an outbreak of equine leukoencephalomalacia. Two samples of the corn consumed by the affected horses contained fumonisin B1 at levels of 46 and 53 µg/g and Fusarium moniliforme, a good in vitro mycotoxin producer.

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Fatty acylation is important but not essential for Saccharomyces cerevisiae RAS function

Molecular and Cellular Biology ◽

10.1128/mcb.7.7.2344-2351.1987 ◽

1987 ◽

Vol 7 (7) ◽

pp. 2344-2351

Author(s):

R J Deschenes ◽

J R Broach

Keyword(s):

Saccharomyces Cerevisiae ◽

Protein Function ◽

Membrane Fraction ◽

Carbon Sources ◽

Fatty Acyl ◽

Yeast Saccharomyces Cerevisiae ◽

Fatty Acyl Moiety ◽

Fatty Acylation ◽

Absolute Requirement

Two proteins in the yeast Saccharomyces cerevisiae that are encoded by the genes RAS1 and RAS2 are structurally and functionally homologous to proteins of the mammalian ras oncogene family. We examined the role of fatty acylation in the maturation of yeast RAS2 protein by creating mutants in the putative palmitate addition site located at the carboxyl terminus of the protein. Two mutations, Cys-318 to an opal termination codon and Cys-319 to Ser-319, were created in vitro and substituted in the chromosome in place of the normal RAS2 allele. These changes resulted in a failure of RAS2 protein to be acylated with palmitate and a failure of RAS2 protein to be localized to a membrane fraction. The mutations yielded a Ras2- phenotype with respect to the ability of the resultant mutants to grow on nonfermentable carbon sources and to complement ras1- mutants. However, overexpression of the ras2Ser-319 product yielded a Ras+ phenotype without a corresponding association of the mutant protein with the membrane fraction. We conclude that the presence of a fatty acyl moiety is important for localizing RAS2 protein to the membrane where it is active but that the fatty acyl group is not an absolute requirement of RAS2 protein function.

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Hydrolyzed fumonisin B1 induces less inflammatory responses than fumonisin B1 in the co-culture model of porcine intestinal epithelial and immune cells

Toxicology Letters ◽

10.1016/j.toxlet.2019.01.013 ◽

2019 ◽

Vol 305 ◽

pp. 110-116 ◽

Cited By ~ 13

Author(s):

Min Jeong Gu ◽

Seung Eun Han ◽

Kyoryen Hwang ◽

Elisabeth Mayer ◽

Nicole Reisinger ◽

...

Keyword(s):

Immune Cells ◽

Inflammatory Responses ◽

Fumonisin B1 ◽

Intestinal Epithelial ◽

Culture Model ◽

Hydrolyzed Fumonisin

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Liquid Chromatographic Determination of Sphmgamne and Sphingosine: Use of the Free Sphinganine-to-Sphingosine Ratio as a Biomarker for Consumption of Fumonisins

Journal of AOAC International ◽

10.1093/jaoac/77.2.533 ◽

1994 ◽

Vol 77 (2) ◽

pp. 533-540 ◽

Cited By ~ 62

Author(s):

Ronald T Riley ◽

Elaine Wang ◽

Alfred H Merrill

Keyword(s):

De Novo ◽

Fumonisin B1 ◽

Chromatographic Determination ◽

Structural Features ◽

Serum Marker ◽

Fungal Culture ◽

Sphingoid Bases ◽

Study Results ◽

Liquid Chromatographic

Abstract Because the chemical structure of fumonisin B1 (FB1) has several structural features in common with the sphingoid bases, sphingosine and dihydro-sphingosine (sphinganine), we tested the hypothesis that the fumonisins might alter the normal cellular activity or the metabolism of endogenous free sphingoid bases. FB1 was found to be a potent inhibitor of de novo sphingolipid biosynthesis in vitro, its primary target being sphinganine N-acyl-transferase. This inhibition resulted in a decrease in the biosynthesis of sphingosine and an accumulation of free sphinganine, an intermediate in the de novo biosynthetic pathway for complex sphin-golipids. These findings led to the hypothesis that consumption of feed containing fumo|nisins should cause an increase in the ratio of free sphinganine to free sphingosine in tissues and serum. Data consistent with this hypothesis have been obtained from horses and pigs that consumed feed containing fumonisin-contaminated corn screenings and from rats fed feed supplemented with fumonisin-containing fungal culture materials or pure FBi. Thus, the ratio of free sphinganine to free sphingosine shows promise as a tissue, urine, or serum marker for animals consuming feed containing fumonisins. The present paper provides a detailed description of the extraction of free sphingoid bases and the liquid chromatographic method we used for determining the relative amounts of free sphingosine and free sphinganine in serum, urine, and various tissues of animals. Study results are summarized, and the ratio of free sphinganine to free sphingosine is discussed as a presumptive test for identifying animals consuming fumonisin-contami-nated feed.

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In Vitro Fumonisin Biosynthesis and Genetic Structure of Fusarium verticillioides Strains from Five Mediterranean Countries

Microorganisms ◽

10.3390/microorganisms8020241 ◽

2020 ◽

Vol 8 (2) ◽

pp. 241 ◽

Cited By ~ 1

Author(s):

Giovanni Beccari ◽

Łukasz Stępień ◽

Andrea Onofri ◽

Veronica M. T. Lattanzio ◽

Biancamaria Ciasca ◽

...

Keyword(s):

Genetic Structure ◽

Geographical Origin ◽

Fusarium Verticillioides ◽

Fumonisin B1 ◽

Genetic Profile ◽

Mediterranean Countries ◽

Intergenic Regions ◽

Fumonisin B2 ◽

High Level

Investigating the in vitro fumonisin biosynthesis and the genetic structure of Fusarium verticillioides populations can provide important insights into the relationships between strains originating from various world regions. In this study, 90 F. verticillioides strains isolated from maize in five Mediterranean countries (Italy, Spain, Tunisia, Egypt and Iran) were analyzed to investigate their ability to in vitro biosynthesize fumonisin B1, fumonisin B2 and fumonisin B3 and to characterize their genetic profile. In general, 80% of the analyzed strains were able to biosynthesize fumonisins (range 0.03–69.84 μg/g). Populations from Italy, Spain, Tunisia and Iran showed a similar percentage of fumonisin producing strains (>90%); conversely, the Egyptian population showed a lower level of producing strains (46%). Significant differences in fumonisin biosynthesis were detected among strains isolated in the same country and among strains isolated from different countries. A portion of the divergent FUM1 gene and of intergenic regions FUM6-FUM7 and FUM7-FUM8 were sequenced to evaluate strain diversity among populations. A high level of genetic uniformity inside the populations analyzed was detected. Apparently, neither geographical origin nor fumonisin production ability were correlated to the genetic diversity of the strain set. However, four strains from Egypt differed from the remaining strains.

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Reproductive and Sphingolipid Metabolic Effects of Fumonisin B1 and its Alkaline Hydrolysis Product in LM/Bc Mice: Hydrolyzed Fumonisin B1 Did Not Cause Neural Tube Defects

Toxicological Sciences ◽

10.1093/toxsci/kfp215 ◽

2009 ◽

Vol 112 (2) ◽

pp. 459-467 ◽

Cited By ~ 52

Author(s):

Kenneth A. Voss ◽

Ronald T. Riley ◽

Maurice E. Snook ◽

Janee Gelineau-van Waes

Keyword(s):

Neural Tube ◽

Neural Tube Defects ◽

Alkaline Hydrolysis ◽

Hydrolysis Product ◽

Fumonisin B1 ◽

Metabolic Effects ◽

Hydrolyzed Fumonisin

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Antifungal Activity of Gepinacin Scaffold Glycosylphosphatidylinositol Anchor Biosynthesis Inhibitors with Improved Metabolic Stability

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00899-20 ◽

2020 ◽

Vol 64 (10) ◽

Author(s):

Sean D. Liston ◽

Luke Whitesell ◽

Catherine A. McLellan ◽

Ralph Mazitschek ◽

Vidmantas Petraitis ◽

...

Keyword(s):

Single Dose ◽

Antifungal Activity ◽

Broad Spectrum ◽

Rabbit Model ◽

Glycosylphosphatidylinositol Anchor ◽

Structure Activity ◽

Biosynthesis Inhibitors ◽

The Stability ◽

Mammalian Toxicity

ABSTRACT The glycosylphosphatidylinositol anchor biosynthesis inhibitor gepinacin demonstrates broad-spectrum antifungal activity and negligible mammalian toxicity in culture but is metabolically labile. The stability and bioactivity of 39 analogs were tested in vitro to identify LCUT-8, a stabilized lead with increased potency and promising single-dose pharmacokinetics. Unfortunately, no antifungal activity was seen at the maximum dosing achievable in a neutropenic rabbit model. Nevertheless, structure-activity relationships identified here suggest strategies to further improve compound potency, solubility, and stability.

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