A key step in the biosynthesis of numerous polyketides is the stereospecific formation of a spiroacetal (spiroketal). We report here that spiroacetal formation in the biosynthesis of the macrocyclic polyketides ossamycin and oligomycin involves catalysis by a novel spiroacetal cyclase. OssO from the ossamycin biosynthetic gene cluster (BGC) is homologous to OlmO, the product of an unannotated gene from the oligomycin BGC. The deletion of olmO abolished oligomycin production and led to the isolation of oligomycin-like metabolites lacking the spiroacetal structure. Purified OlmO catalyzed complete conversion of the major metabolite into oligomycin C. Crystal structures of OssO and OlmO reveal an unusual 10-strand β-barrel. Three conserved polar residues are clustered together in the β-barrel cavity, and site-specific mutation of any of these residues either abolished or substantially diminished OlmO activity, supporting a role for general acid/general base catalysis in spiroacetal formation.

中文翻译：

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聚酮类抗生素生物合成中的酶催化螺缩醛形成

许多聚酮化合物的生物合成中的一个关键步骤是螺缩醛（螺缩酮）的立体定向形成。我们在此报告大环聚酮化合物骨霉素和寡霉素的生物合成中的螺缩醛形成涉及新型螺缩醛环化酶的催化。来自骨霉素生物合成基因簇 (BGC) 的 OssO 与 OlmO 同源，OlmO 是寡霉素 BGC 的未注释基因的产物。删除olmO消除了寡霉素的产生并导致分离出缺乏螺缩醛结构的寡霉素样代谢物。纯化的OlmO 催化主要代谢物完全转化为寡霉素C。OssO 和OlmO 的晶体结构揭示了一个不寻常的10 链β-桶。三个保守的极性残基在 β-桶形腔中聚集在一起，并且这些残基中的任何一个的位点特异性突变都消除或大大降低了 OlmO 活性，支持一般酸/一般碱催化在螺缩醛形成中的作用。