非典型角蒽环聚酮氧化开环酶的功能与进化

非典型角蒽环聚酮化合物是一类经过氧化重排反应形成的具有独特骨架结构的芳香聚酮类化合物。近年来的研究表明,尽管此类化合物具有多种多样的骨架结构,它们都是由共同的生物合成中间体Dehydrorabelomycin生成的。一个独特的加氧酶家族(称为非典型角蒽环氧化开环酶)催化了Dehydrorabelomycin的氧化碳-碳键断裂与重排反应。尽管这些酶属于同一个蛋白质家族,催化相同的底物发生氧化开环反应,但是通过不同的重排方式形成了对应于各自生物合成终产物的骨架结构,对这类化合物最终结构的形成起到了关键作用。对这一家族的加氧酶进行深入的催化功能与反应机理研究,不仅有助于对已知芳香聚酮的结构改造与新颖骨架结构芳香聚酮的发现,也有助于加深对于蛋白质序列进化与功能演化的认识。

Catalysis and evolution of the ring-opening oxygenases in biosynthesis of atypical angucyclines

Atypical angucyclines are a class of aromatic polyketides with unique structures and formed via oxidative rearrangement reactions. Recent studies have demonstrated that their various skeletons are derived from a common biosynthetic intermediate dehydrorabelomycin. A unique family of oxygenases, atypical angucycline ring-opening oxygenases, catalyzes the oxidative carbon-carbon bond cleavage and rearrangement reactions of dehydrorabelomycin, which is a critical step in the biosynthesis of these compounds. Although these ring-opening oxygenases belong to the same protein family, and catalyze the oxidative ring-opening reaction of the same substrate dehydrorabelomycin, different rearrangement reactions render different structures of the products, which are consistent with the skeletons of their final products. The in-depth study on the catalysis of this family of oxygenases will not only contribute to the structural modification of known aromatic polyketides and the discovery of polyketides with novel skeletons, but also help to deepen our understanding of protein sequence evolution and functional diversities.