title: Novel cysteine-centered sulfur metabolic pathway in the thermotolerant methylotrophic yeast Hansenula polymorpha.
abstract: In yeast and filamentous fungi, sulfide can be condensed either with O-acetylhomoserine to generate homocysteine, the precursor of methionine, or with O-acetylserine to directly generate cysteine. The resulting homocysteine and cysteine can be interconverted through transsulfuration pathway. Here, we systematically analyzed the sulfur metabolic pathway of the thermotolerant methylotrophic yeast Hansenula polymorpha, which has attracted much attention as an industrial yeast strain for various biotechnological applications. Quite interestingly, the detailed sulfur metabolic pathway of H. polymorpha, which was reconstructed based on combined analyses of the genome sequences and validation by systematic gene deletion experiments, revealed the absence of de novo synthesis of homocysteine from inorganic sulfur in this yeast. Thus, the direct biosynthesis of cysteine from sulfide is the only pathway of synthesizing sulfur amino acids from inorganic sulfur in H. polymorpha, despite the presence of both directions of transsulfuration pathway Moreover, only cysteine, but no other sulfur amino acid, was able to repress the expression of a subset of sulfur genes, suggesting its central and exclusive role in the control of H. polymorpha sulfur metabolism. 35S-Cys was more efficiently incorporated into intracellular sulfur compounds such as glutathione than 35S-Met in H. polymorpha, further supporting the cysteine-centered sulfur pathway. This is the first report on the novel features of H. polymorpha sulfur metabolic pathway, which are noticeably distinct from those of other yeast and filamentous fungal species.
authors: Department of Life Science, Chung-Ang University, Seoul, Korea; Department of Chemical & Biomolecular Engineering (BK21+ program), Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea.
authors: Min Jeong
authors: MJ
authors: Sohn
authors: Department of Life Science, Chung-Ang University, Seoul, Korea.
authors: Su Jin
authors: SJ
authors: Yoo
authors: Biochemicals and Synthetic Biology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Korea.
authors: Doo-Byoung
authors: DB
authors: Oh
authors: Biochemicals and Synthetic Biology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Korea.
authors: Ohsuk
authors: O
authors: Kwon
authors: Department of Chemical & Biomolecular Engineering (BK21+ program), Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea.
authors: Sang Yup
authors: SY
authors: Lee
authors: Institute of Cell Biology, National Academy of Sciences of Ukraine, Lviv, Ukraine.
authors: Andriy A
authors: AA
authors: Sibirny
authors: Department of Life Science, Chung-Ang University, Seoul, Korea.
authors: Hyun Ah
authors: HA
authors: Kang
mesh_terms: D000595:Amino Acid Sequence; D000603:Amino Acids, Sulfur / Q000378:metabolism; D002244:Carbon / Q000378:metabolism; D003545:Cysteine / Q000378:metabolism*; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017353:Gene Deletion; D005978:Glutathione / Q000096:biosynthesis; D053858:Metabolic Networks and Pathways; D008969:Molecular Sequence Data; D009154:Mutation; D010843:Pichia / Q000235:genetics / Q000378:metabolism*; D015203:Reproducibility of Results; D016415:Sequence Alignment; D012694:Serine / Q000031:analogs & derivatives / Q000378:metabolism; D013455:Sulfur / Q000378:metabolism*
chemical_list: D000603:Amino Acids, Sulfur; D005656:Fungal Proteins; D012694:Serine; D013455:Sulfur; D002244:Carbon; C043943:O-acetylserine; D005978:Glutathione; D003545:Cysteine