A1 Refereed original research article in a scientific journal
Biosynthetic Conclusions from the Functional Dissection of Oxygenases for Biosynthesis of Actinorhodin and Related Streptomyces Antibiotics
Authors: Taguchi T, Yabe M, Odaki H, Shinozaki M, Metsa-Ketela M, Arai T, Okamoto S, Ichinose K
Publisher: CELL PRESS
Publication year: 2013
Journal: Chemistry and Biology
Journal name in source: CHEMISTRY & BIOLOGY
Journal acronym: CHEM BIOL
Number in series: 4
Volume: 20
Issue: 4
First page : 510
Last page: 520
Number of pages: 11
ISSN: 1074-5521
DOI: https://doi.org/10.1016/j.chembiol.2013.03.007
Abstract
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.
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.
UTU Research Portal