Clonostachys rosea demethiolase STR3 controls the conversion of methionine into methanethiol
| Autor: | Ya-Jie Tang, Quan Zhang, Kai-Zhi Jia, Lin-Yang Sun, Yang-Hua Xu, Hong-Mei Li |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Transamination 030106 microbiology Gene Expression Methanethiol Biology Article Mass Spectrometry Substrate Specificity Fungal Proteins 03 medical and health sciences chemistry.chemical_compound Methionine Downregulation and upregulation Gene expression Amino Acid Sequence Sulfhydryl Compounds chemistry.chemical_classification Fungal protein Multidisciplinary Recombinant Proteins Culture Media Carbon-Sulfur Lyases 030104 developmental biology Enzyme Biochemistry chemistry Saccharomycetales Ketoglutaric Acids Sequence Alignment Intracellular psychological phenomena and processes Chromatography Liquid |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep21920 |
| Popis: | Eukaryote-derived methioninase, catalyzing the one-step degradation of methionine (Met) to methanethiol (MTL), has received much attention for its low immunogenic potential and use as a therapeutic agent against Met-dependent tumors. Although biological and chemical degradation pathways for Met-MTL conversion are proposed, the concrete molecular mechanism for Met-MTL conversion in eukaryotes is still unclear. Previous studies demonstrated that α-keto-methylthiobutyric acid (KMBA), the intermediate for Met-MTL conversion, was located extracellularly and the demethiolase STR3 possessed no activities towards Met, which rule out the possibility of intracellular Met-MTL conversion pathway inside eukaryotes. We report here that degradation of Met resulted in intracellular accumulation of KMBA in Clonostachys rosea. Addition of Met to culture media led to the production of MTL and downregulation of STR3, while incubation of Met with surrogate substrate α-ketoglutaric acid enhanced the synthesis of MTL and triggered the upregulation of STR3. Subsequent biochemical analysis with recombinant STR3 showed that STR3 directly converted both Met and its transamination product KMBA to MTL. These results indicated that STR3 as rate-limiting enzyme degrades Met and KMBA into MTL. Our findings suggest STR3 is a potential target for therapeutic agents against Met-dependent tumors and aging. |
| Databáze: | OpenAIRE |
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