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Biosynthetic Conclusions from the Functional Dissection of Oxygenases for Biosynthesis of Actinorhodin and Related Streptomyces Antibiotics
- Source :
- Chemistry & Biology. 20:510-520
- Publication Year :
- 2013
- Publisher :
- Elsevier BV, 2013.
-
Abstract
- SummaryActinorhodin (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 AlnT) 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 AlnT, which is involved in lateral p-quinone formation in ALN.
- Subjects :
- Spectrometry, Mass, Electrospray Ionization
Stereochemistry
Clinical Biochemistry
Anthraquinones
Flavin group
01 natural sciences
Biochemistry
Streptomyces
Actinorhodin
Mixed Function Oxygenases
Hydroxylation
03 medical and health sciences
chemistry.chemical_compound
Bacterial Proteins
Biosynthesis
Oxidoreductase
Drug Discovery
NADH, NADPH Oxidoreductases
Molecular Biology
Chromatography, High Pressure Liquid
030304 developmental biology
Pharmacology
chemistry.chemical_classification
0303 health sciences
biology
010405 organic chemistry
Streptomyces coelicolor
Quinones
ta1182
General Medicine
Monooxygenase
biology.organism_classification
Recombinant Proteins
Anti-Bacterial Agents
3. Good health
0104 chemical sciences
chemistry
Multigene Family
Molecular Medicine
Naphthoquinones
Subjects
Details
- ISSN :
- 10745521
- Volume :
- 20
- Database :
- OpenAIRE
- Journal :
- Chemistry & Biology
- Accession number :
- edsair.doi.dedup.....0990d37933a65a2d6142ea5636643362