期刊
CHEMISTRY & BIOLOGY
卷 20, 期 4, 页码 510-520出版社
CELL PRESS
DOI: 10.1016/j.chembiol.2013.03.007
关键词
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资金
- Ministry of Education, Culture, Sports, Science and Technology of Japan [23108526]
- Academy of Finland [136060]
- Japan Society for the Promotion of Science [20580091, 2465125]
- Grants-in-Aid for Scientific Research [24580131, 20580091] Funding Source: KAKEN
Actinorhodin (ACT) produced by Streptomyces coelicolor A3(2) belongs to the benzoisochromanequinone (BIQ) class of antibiotics. ActVA-ORF5, a flavin-dependent monooxygenase (FMO) essential for ACT biosynthesis, forms a two-component enzyme system in combination with a flavin:NADH oxidoreductase, ActVB. The genes for homologous two-component FMOs are found in the biosynthetic gene clusters for two other BIQs, granaticin (GRA) and medermycin (MED), and a closely related antibiotic, alnumycin (ALN). Our functional analysis of these FMOs (ActVA-ORF5, Gra-ORF21, Med-ORF7, and AInT) in S. coelicolor unambiguously demonstrated that ActVA-ORF5 and Gra-ORF21 are bifunctional and capable of both p-quinone formation at C-6 in the central ring and C-8 hydroxylation in the lateral ring, whereas Med-ORF7 catalyzes only p-quinone formation. No p-quinone formation on a BIQ substrate was observed for AInT, which is involved in lateral p-quinone formation in ALN.
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