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Identification and characterization of a sulfite reductase gene and new insights regarding the sulfur-containing amino acid metabolism in the basidiomycetous yeast Cryptococcus neoformans
Current Genetics ( IF 2.5 ) Pub Date : 2020-10-01 , DOI: 10.1007/s00294-020-01112-9
Phuong-Thao Nguyen 1, 2 , Akio Toh-E 3 , Ngoc-Hung Nguyen 1, 2 , Yumi Imanishi-Shimizu 4 , Akira Watanabe 3 , Katsuhiko Kamei 3 , Kiminori Shimizu 1, 3
Affiliation  

The amino acid biosynthetic pathway of invasive pathogenic fungi has been studied as a potential antifungal drug target. Studies of the disruption of genes involved in amino acid biosynthesis have demonstrated the importance of this pathway in the virulence of Cryptococcus neoformans. Here, we identified the MET5 (CNL05500) and MET10 (CNG03990) genes in this pathway, both encoding sulfite reductase, which catalyzes the reduction of sulfite to sulfide. The MET14 (CNE03880) gene was also identified, which is responsible for the conversion of sulfate to sulfite. The use of cysteine as a sulfur source led to the production of methionine via hydrogen sulfide synthesis mediated by CYS4 (CNA06170), CYS3 (CNN01730), and MST1 (CND03690). MST1 exhibited high homology with the TUM1 gene of Saccharomyces cerevisiae, which has functional similarity with the 3-mercaptopyruvate sulfurtransferase (3-MST) gene in humans. Although the hypothesis that hydrogen sulfide is produced from cysteine via CYS4, CYS3, and MST1 warrants further study, the new insight into the metabolic pathway of sulfur-containing amino acids in C. neoformans provided here indicates the usefulness of this system in the development of screening tools for antifungal drug agents.



中文翻译:

亚硫酸还原酶基因的鉴定和表征以及新孢子菌酵母隐球菌中含硫氨基酸代谢的新见解

入侵性致病真菌的氨基酸生物合成途径已被研究为潜在的抗真菌药物靶标。对参与氨基酸生物合成的基因的破坏研究表明,该途径在新型隐球菌的毒性中的重要性。在这里,我们确定了该途径中的MET5CNL05500)和MET10CNG03990)基因,均编码亚硫酸还原酶,该酶催化亚硫酸盐还原为硫化物。该MET14CNE03880)基因也被鉴定,其负责硫酸盐向亚硫酸盐的转化。使用半胱氨酸作为硫源导致通过由CYS4CNA06170,CYS3CNN01730)和MST1CND03690)介导的硫化氢合成产生蛋氨酸。MST1酿酒酵母TUM1基因具有高度同源性,在人类中它与3-巯基丙酮酸硫转移酶(3-MST)基因具有功能相似性。尽管关于半胱氨酸通过CYS4CYS3CYS3产生硫化氢的假设MST1值得进一步研究,新的洞察含硫氨基酸,代谢途径隐球菌此处提供证明此系统的筛选工具抗真菌药剂的发展的作用。

更新日期:2020-10-02
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