Research Institute of Pharmaceutical Sciences, Musashino University, 1-1-20, Shinmachi, Nishitokyo-shi, Tokyo, 202-8585, Japan.
National Institute of Health Sciences, 3-25-26, Tonomachi, Kawasaki-ku, Kawasaki-shi, Kanagawa, 210-9501, Japan.
Chembiochem. 2020 Mar 2;21(5):623-627. doi: 10.1002/cbic.201900490. Epub 2019 Nov 27.
Flavin-dependent monooxygenases are ubiquitous in living systems and are classified into single- or two-component systems. Actinorhodin, produced by Streptomyces coelicolor, is a representative polycyclic polyketide that is hydroxylated through the action of the two-component ActVA-5/ActVB hydroxylase system. These homologous systems are widely distributed in bacteria, but their reaction mechanisms remain unclear. This in vitro investigation has provided chemical proof of two consecutive hydroxylations via hydroxynaphthalene intermediates involved in actinorhodin biosynthesis. The ActVA-5 oxygenase component catalyzed a stepwise dihydroxylation of the substrate, whereas the ActVB flavin reductase not only supplied a reduced cofactor, but also regulated the quinone-hydroquinone interconversion of an intermediate. Our study provides clues for understanding the general biosynthetic mechanisms of highly functionalized aromatic natural products with structural diversity.
黄素依赖单加氧酶在生命系统中普遍存在，分为单组分或双组分系统。放线紫红素是由变铅青链霉菌产生的一种典型的多环聚酮化合物，通过双组分 ActVA-5/ActVB 羟化酶系统进行羟化。这些同源系统广泛分布于细菌中，但它们的反应机制尚不清楚。本体外研究通过涉及放线紫红素生物合成的羟基萘中间体，提供了两个连续羟基化的化学证据。ActVA-5 加氧酶组分催化底物的逐步二羟化，而 ActVB 黄素还原酶不仅提供了还原辅助因子，还调节了中间产物的醌-氢醌互变。我们的研究为理解具有结构多样性的高度官能化芳香天然产物的一般生物合成机制提供了线索。
