Biosynthesis of Actinorhodin and Related Antibiotics: Discovery of Alternative Routes for Quinone Formation Encoded in the act Gene Cluster
Biosynthesis of Actinorhodin and Related Antibiotics: Discovery of Alternative Routes for Quinone Formation Encoded in the act Gene Cluster
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DOI：
10.1016/j.chembiol.2009.01.015
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发表时间：
2009-02-27
影响因子：
--
通讯作者：
Ichinose, Koji
中科院分区：
文献类型：
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作者：
Okamoto, Susumu;Taguchi, Takaaki;Ichinose, Koji
所有已知的苯并异色满醌（BIQ）生物合成基因簇都携带一组编码双组分单加氧酶的基因，该基因与天蓝色链霉菌A3中用于放线菌紫素生物合成的ActVA-ORF 5/ActVB系统同源（2）。在这里，我们进行了这种酶系统的分子遗传学和生物化学研究。actVA-ORF 5的失活产生了分流产物放线菌酮（ACPL），显然衍生自6-脱氧-二氢-卡拉芬净。类似地，actVB的缺失导致ACPL的积累，表明单加氧酶系统在C-6氧合中的关键作用，这是所有BIQ生物合成共同的生物合成步骤。此外，在体外，我们显示了醌形成活性的ActVA-ORF 5/ActVB系统除了一个已知的C-6单加氧酶，ActVA-ORF 6，通过使用emodinanthrone作为模型底物。我们的研究结果表明，行为基因簇编码两种替代途径的醌形成的C-6氧化BIQ生物合成。
All known benzoisochromanequinone (BIQ) biosynthetic gene clusters carry a set of genes encoding a two-component monooxygenase homologous to the ActVA-ORF5/ActVB system for actinorhodin biosynthesis in Streptomyces coelicolor A3(2). Here, we conducted molecular genetic and biochemical studies of this enzyme system. Inactivation of actVA-ORF5 yielded a shunt product, actinoperylone (ACPL), apparently derived from 6-deoxy-dihydro-kalafungin. Similarly, deletion of actVB resulted in accumulation of ACPL, indicating a critical role for the monooxygenase system in C-6 oxygenation, a biosynthetic step common to all BIQ biosyntheses. Furthermore, in vitro, we showed a quinone-forming activity of the ActVA-ORF5/ActVB system in addition to that of a known C-6 monooxygenase, ActVA-ORF6, by using emodinanthrone as a model substrate. Our results demonstrate that the act gene cluster encodes two alternative routes for quinone formation by C-6 oxygenation in BIQ biosynthesis.