Disruption of six <i>Saccharomyces cerevisiae</i> ORFs on chromosome XII results in three lethal disruptants

Alloush, Habib M.; Edwards, Thomas A.; Valle-Lisboa, Virginia; Wheals, Alan E.

doi:10.1002/yea.808

Cited by 2 publications

(2 citation statements)

References 27 publications

(28 reference statements)

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“…Gene Deletion Standard methods for DNA manipulations were referring as described by Brachmann et al 27,28) Briefly, S. cerevisiae S288C genomic DNA was used as the template. pTEF1/Zeo was used as the manipulated plasmid.…”

Section: Methodsmentioning

confidence: 99%

Identification of Y118 Amino Acid Residue in Candida albicans Sterol 14.ALPHA.-Demethylase Associated with the Enzyme Activity and Selective Antifungal Activity of Azole Analogues

Chen

Sheng

et al. 2007

Biological & Pharmaceutical Bulletin

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Azoles are widely used in the treatment of fungal infections. They act by competitive inhibition of lanosterol 14a-demethylase (P45014DM, CYP51), the key enzyme in sterol biosynthesis, which results in depletion of ergosterol and accumulation of lanosterol and other 14-methyl sterols ultimately leading to the growth inhibition of fungal cells.1) Inhibition of the ergosterol biosynthetic pathway in fungi has thus attracted intense interests in the application of such antifungal compounds. However, it was found in the past two decades that azole resistance often develops prolonged use of oral imidazole and triazole, or different forms of immunodeficiency in fungal infection patients.2) Furthermore, cross inhibition of CYP51 in different species also causes undesirable side effects.3) It is, therefore, of increasingly interest to develop novel antifungal agents with more selective antifungal activity, higher efficiency, broader pectrum, and lower toxicity.Azole antifungal agents inhibit the CYP51 by a mechanism in which the heterocyclic nitrogen atom (N-3 of imidazole and N-4 of triazole) binds to the heme iron atom in the binding site of the enzyme. Because all the fungal CYP51 proteins that had been characterized were membrane-bound and difficult to solve their crystal structures, the study of the interaction between azoles and fungal CYP51 can only be done by methods of molecular modeling. Several three-dimensional (3D) models of CYP51 and their interaction with azole antifungal agents has been reported. Ji et al. 3,4) built a homologous 3D model of CYP51 from C. albicans based on the crystal coordinates of all four known prokaryotic P450s. With this model they found that the halogenated phenyl group of azole inhibitors is deep in the hydrophobic binding cleft and the long side chains of some inhibitors such as itraconazole and ketoconazole surpass the active site and interact with the residues in the substrate access channel. Another 3D molecular model constructed by Lewis et al. 5) also showed that typical azole inhibitors were able to fit the putative active site of CYP51 by a combination of heme coordination, hydrogen bonding, p-p stacking and hydrophobic interactions within the heme environment of the enzymes. Recently, modelling data of Li et al. 6) suggest that the long chain of posaconazole and itraconazole occupies a specific channel within CYP51 and that this additional interaction serves to stabilize the binding of these azoles to the mutated CYP51 proteins. Models generated by Fukuoka et al. 7) predicted that voriconazole was a more potent inhibitor than fluconazole because the additional methyl group of voriconazole resulted in stronger hydrophobic interaction with the aromatic amino acids in the substrate binding site and filled the site more extensively.In our studies, the 3D model of CYP51 from Candida albicans (CACYP51) was constructed.3) In addition, the binding mode of the substrate with fungal CYP51 was also investigated.3) In order to search more potent azoles antifungal agents and desi...

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Section: Methodsmentioning

confidence: 99%

Identification of Y118 Amino Acid Residue in Candida albicans Sterol 14.ALPHA.-Demethylase Associated with the Enzyme Activity and Selective Antifungal Activity of Azole Analogues

Chen

Sheng

et al. 2007

Biological & Pharmaceutical Bulletin

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“…The transcriptional reprogramming of yeast in response to oxidative stress is mainly regulated by two oxidative stress-responsive transcription factors, Yap1 and Skn7, and the general stress transcription factors, Msn2/Msn4 (Auesukaree, 2017). Notably, Skn7 has an important role in the regulation of genes involved in the maintenance of cell wall integrity, including genes coding for CWPs (Alloush et al, 2002;Li et al, 2002;Levin, 2011). The CWI pathway sensors Wsc1, Wsc2, Mtl1, and Mid2 play an important role in the sensing of oxidative stress induced by H 2 O 2 (Vilella et al, 2005;Jin et al, 2013;Vélez-Segarra et al, 2020).…”

Section: Yeast Response and Tolerance To Industrially Relevant Stress...mentioning

confidence: 99%

The cell wall and the response and tolerance to stresses of biotechnological relevance in yeasts

2022

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In industrial settings and processes, yeasts may face multiple adverse environmental conditions. These include exposure to non-optimal temperatures or pH, osmotic stress, and deleterious concentrations of diverse inhibitory compounds. These toxic chemicals may result from the desired accumulation of added-value bio-products, yeast metabolism, or be present or derive from the pre-treatment of feedstocks, as in lignocellulosic biomass hydrolysates. Adaptation and tolerance to industrially relevant stress factors involve highly complex and coordinated molecular mechanisms occurring in the yeast cell with repercussions on the performance and economy of bioprocesses, or on the microbiological stability and conservation of foods, beverages, and other goods. To sense, survive, and adapt to different stresses, yeasts rely on a network of signaling pathways to modulate the global transcriptional response and elicit coordinated changes in the cell. These pathways cooperate and tightly regulate the composition, organization and biophysical properties of the cell wall. The intricacy of the underlying regulatory networks reflects the major role of the cell wall as the first line of defense against a wide range of environmental stresses. However, the involvement of cell wall in the adaptation and tolerance of yeasts to multiple stresses of biotechnological relevance has not received the deserved attention. This article provides an overview of the molecular mechanisms involved in fine-tuning cell wall physicochemical properties during the stress response of Saccharomyces cerevisiae and their implication in stress tolerance. The available information for non-conventional yeast species is also included. These non-Saccharomyces species have recently been on the focus of very active research to better explore or control their biotechnological potential envisaging the transition to a sustainable circular bioeconomy.

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Disruption of six Saccharomyces cerevisiae ORFs on chromosome XII results in three lethal disruptants

Cited by 2 publications

References 27 publications

Identification of Y118 Amino Acid Residue in Candida albicans Sterol 14.ALPHA.-Demethylase Associated with the Enzyme Activity and Selective Antifungal Activity of Azole Analogues

Identification of Y118 Amino Acid Residue in Candida albicans Sterol 14.ALPHA.-Demethylase Associated with the Enzyme Activity and Selective Antifungal Activity of Azole Analogues

The cell wall and the response and tolerance to stresses of biotechnological relevance in yeasts

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