Chitin Biosynthesis in Fungi

Ruiz-Herrera, Jos√©; Ruíz-Medrano, Roberto

doi:10.1201/9780203027356.ch24

Cited by 15 publications

(23 citation statements)

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“…This taxonomic difference provides the rationale for considering chitin as a safe and largely selective target for developing antifungal control agents (Cohen, 1990). Chitin synthases (CSs) catalyse the transfer of N-acetylglucosamine from uridine diphosphate N-acetylglucosamine (UDPGlcNAc) to a growing chain of b(1,4)-linked Nacetylglucosamine residues (chitin) (Ruiz-Herrera et al, 1992). The specific mechanism by which this polymer is synthesized in vivo by the different species appears to have selective characteristics.…”

Section: Introductionmentioning

confidence: 99%

Role of chitin synthase genes in Fusarium oxysporum

Martin-Udiroz

2004

Microbiology

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Three structural chitin synthase genes, chs1, chs2 and chs3, were identified in the genome of Fusarium oxysporum f. sp. lycopersici, a soilborne pathogen causing vascular wilt disease in tomato plants. Based on amino acid identities with related fungal species, chs1, chs2 and chs3 encode structural chitin synthases (CSs) of class I, class II and class III, respectively. A gene (chs7) encoding a chaperone-like protein was identified by comparison of the deduced protein with Chs7p from Saccharomyces cerevisiae, an endoplasmic reticulum (ER) protein required for the export of ScChs3p (class IV) from the ER. So far no CS gene belonging to class IV has been isolated from F. oxysporum, although it probably contains more than one gene of this class, based on the genome data of the closely related species Fusarium graminearum. F. oxysporum chs1-, chs2-and chs7-deficient mutants were constructed through targeted gene disruption by homologous recombination. No compensatory mechanism seems to exist between the CS genes studied, since chitin content determination and expression analysis of the chs genes showed no differences between the disruption mutants and the wild-type strain. By fluorescence microscopy using Calcofluor white and DAPI staining, the wild-type strain and Dchs2 and Dchs7 mutants showed similar septation and even nuclear distribution, with each hyphal compartment containing only one nucleus, whereas the Dchs1 mutant showed compartments containing up to four nuclei. Pathogenicity assays on tomato plants indicated reduced virulence of Dchs2 and Dchs7 null mutants. Stress conditions affected normal development in Dchs2 but not in Dchs1 or Dchs7 disruptants, and the three chs-deficient mutants showed increased hyphal hydrophobicity compared to the wild-type strain when grown in sorbitol-containing medium. The chitin synthase mutants will be useful for elucidating cell wall biogenesis in F. oxysporum and the relationship between fungal cell wall integrity and pathogenicity. INTRODUCTIONChitin, an important structural cell wall component in many species of yeast and filamentous fungi but absent from plants and vertebrates, is a b(1,4)-linked polymer of N-acetylglucosamine which forms a fibrous polysaccharide. This taxonomic difference provides the rationale for considering chitin as a safe and largely selective target for developing antifungal control agents (Cohen, 1990). Chitin synthases (CSs) catalyse the transfer of N-acetylglucosamine from uridine diphosphate N-acetylglucosamine (UDPGlcNAc) to a growing chain of b(1,4)-linked Nacetylglucosamine residues (chitin) (Ruiz-Herrera et al., 1992). The specific mechanism by which this polymer is synthesized in vivo by the different species appears to have selective characteristics. Fungal CSs are integral membranebound proteins that participate in the biosynthesis of the cell wall and are important for hyphal growth and differentiation (reviewed by Cabib et al., 1996;Roncero, 2002). Comparative analysis of the amino acid sequences deduced from fungal chs genes revea...

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Section: Introductionmentioning

confidence: 99%

Role of chitin synthase genes in Fusarium oxysporum

Martin-Udiroz

2004

Microbiology

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“…Even apparently unimportant CHS genes may be beneficial under stress conditions. We have reported that a chs3 mutant from U. maydis has about the same rate of growth than the wild-type strain when grown together in liquid medium, but is almost completely eliminated when competing into the host [65]. Accordingly, we may suggest that for most Chsps, gene multiplicity probably represents a fail-safe mechanism that allows fungal survival in hostile environments, through their selective regulation [57,66].…”

Section: Multigenic Control Of Chitin Synthases In Fungimentioning

confidence: 95%

Chitin Synthesis as a Target for Antifungal Drugs

Ruiz-Herrera¹,

San-Blas

2003

CDTID

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Human mycoses have become a threat to health world-wide. Unfortunately there are only a limited number of antimycotic drugs in use. Promising targets for drugs specific against fungi are those affecting chitin synthesis. Chitin is absent in vertebrates, and is essential for fungal wall integrity. A thorough knowledge of the mechanism of chitin synthesis is required to design specific inhibitors. We review here our current understanding of the process, and the most promising drugs that inhibit it. Chitin is made by chitin synthases requiring specific microvesicles, the chitosomes, for intracellular transport. Fungi contain several chitin synthases, some of which may be essential at a certain stage. This phenomenon is important to take into account for drug design. The most widely studied chitin synthase inhibitors are polyoxins and nikkomycins that probably bind to the catalytic site of chitin synthases. These are not equally susceptible to the drugs. In Saccharomyces cerevisiae the order of sensitivity is: Chs3p>Chs1p>Chs2p. Main problems for their succesful use in vivo are: low permeability, and different susceptibility of fungal species, and variable responses in animal models. Chemical modifications have been proposed to make more potent derivatives. Other synthetic or natural compounds are also promising as possible inhibitors, but their properties are less well known. Rational drug design has proceeded only on the basis of existing inhibitors, because the structure of the active site of chitin synthase is unknown. Undoubtedly, determination of this, and the biosynthetic mechanism will reveal unexpected drug targets in the future.

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“…Mutations that eliminate the capacity to synthesize chitin are lethal [3,4]. Chitin synthetase utilizes the nucleotide UDP-GlcNAc as sugar donor, and requires a divalent metal ion for activity [2]. Three chitin synthetase activities (CSI, CSII, and CSIII) have been described with distinct function.…”

Section: Introductionmentioning

confidence: 99%

“…Chitin is a polysaccharide made of N-acetylglucosamine (GlcNAc) units joined through b (14) glycosidic linkages. Although it is present in variable proportions, this amino polymer is indispensable for the construction of the cell wall, and therefore, for fungal survival [2]. Inhibition of chitin polymerisation by Polyoxin D, Nikkomycin or Calcofluor White affects septum formation, cell wall maturation and bud ring formation, damaging cell growth by this way.…”

Section: Introductionmentioning

confidence: 99%