Pentaketide Melanin Biosynthesis in Aspergillus fumigatus Requires Chain-length Shortening of a Heptaketide Precursor
| Autor: | Yoshinori Yasuoka, Isao Fujii, Yun C. Chang, Kyung J. Kwon-Chung, Huei-Fung Tsai, Akira Watanabe, Yutaka Ebizuka, Michael H. Wheeler |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Genotype
Genes Fungal Naphthols Reductase Biochemistry Aspergillus fumigatus Polyketide Pigment Bacterial Proteins Multienzyme Complexes Melanin biosynthesis Molecular Biology Gene Chromatography High Pressure Liquid Melanins Cell-Free System ATP synthase biology Cell Biology Spores Fungal biology.organism_classification Enzyme assay Alcohol Oxidoreductases Phenotype Multigene Family visual_art biology.protein visual_art.visual_art_medium Gene Deletion |
| Zdroj: | Journal of Biological Chemistry. 276:29292-29298 |
| ISSN: | 0021-9258 |
| Popis: | Chain lengths and cyclization patterns of microbial polyketides are generally determined by polyketide synthases alone. Fungal polyketide melanins are often derived from a pentaketide 1,8-dihydroxynaphthalene, and pentaketide synthases are used for synthesis of the upstream pentaketide precursor, 1,3,6,8-tetrahydroxynaphthalene (1,3,6,8-THN). However, Aspergillus fumigatus, a human fungal pathogen, uses a heptaketide synthase (Alb1p) to synthesize its conidial pigment through a pentaketide pathway similar to that which produces 1,8-dihydroxynaphthalene-melanin. In this study we demonstrate that a novel protein, Ayg1p, is involved in the formation of 1,3,6,8-THN by chain-length shortening of a heptaketide precursor in A. fumigatus. Deletion of the ayg1 gene prevented the accumulation of 1,3,6,8-THN suggesting the involvement of ayg1 in 1,3,6,8-THN production. Genetic analyses of double-gene deletants suggested that Ayg1p catalyzes a novel biosynthetic step downstream of Alb1p and upstream of Arp2p (1,3,6,8-THN reductase). Further genetic and biochemical analyses of the reconstituted strains carrying alb1, ayg1, or alb1 + ayg1 indicated that Ayg1p is essential for synthesis of 1,3,6,8-THN in addition to Alb1p. Cell-free enzyme assays, using the crude Ayg1p protein extract, revealed that Ayg1p enzymatically shortened the heptaketide product of Alb1p to 1,3,6,8-THN. Thus, the protein Ayg1p facilitates the participation of a heptaketide synthase in a pentaketide pathway via a novel polyketide-shortening mechanism in A. fumigatus. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|