Taguchi Takaaki, Yabe Masaki, Odaki Hitomi, Shinozaki Miki, Metsä-Ketelä Mikko, Arai Takao, Okamoto Susumu, Ichinose Koji
Research Institute of Pharmaceutical Sciences, Musashino University, Shinmachi, Nishitokyo-shi, Tokyo 202-8585, Japan.
Chem Biol. 2013 Apr 18;20(4):510-20. doi: 10.1016/j.chembiol.2013.03.007.
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 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.
天蓝色链霉菌A3(2)产生的放线紫红素（ACT）属于苯并异色满醌（BIQ）类抗生素。ActVA-ORF5是ACT生物合成所必需的一种黄素依赖性单加氧酶（FMO），它与黄素：NADH氧化还原酶ActVB形成一个双组分酶系统。在另外两种BIQ（石榴霉素（GRA）和美登霉素（MED））以及一种密切相关的抗生素铝霉素（ALN）的生物合成基因簇中发现了同源双组分FMO的基因。我们对天蓝色链霉菌中这些FMO（ActVA-ORF5、Gra-ORF21、Med-ORF7和AlnT）的功能分析明确表明，ActVA-ORF5和Gra-ORF21具有双功能，能够在中环的C-6位形成对醌以及在侧环的C-8位进行羟基化，而Med-ORF7仅催化对醌的形成。对于参与ALN侧链对醌形成的AlnT，未观察到其在BIQ底物上形成对醌。
