A novel quinone-forming monooxygenase family involved in modification of aromatic polyketides
A novel quinone-forming monooxygenase family involved in modification of aromatic polyketides
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DOI：
10.1074/jbc.m500190200
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发表时间：
2005-04-15
影响因子：
4.8
通讯作者：
Horinouchi, S
中科院分区：
文献类型：
--
作者：
Funa, N;Funabashi, M;Horinouchi, S
RppA是一种III型聚酮合成酶（PKS），它催化5个丙二酰辅酶a分子缩合形成1,3,6,8-四羟基萘（THN）。在链霉菌IFO13271和其他几种链霉菌中，一个名为momA的开放阅读框作为rppA的邻居存在。MomA属于“杯形”超家族，因为它包含一组两个基元，负责结合一个相当于金属离子的基元。MomA通过RppA的作用催化丙二酰辅酶a产生的THN的单氧作用形成flaviolin。此外，它还以几种聚酮为底物，形成了相应的醌类化合物。MomA的活性需要氧化还原活性过渡金属离子（Ni2+、Cu2+、Fe3+、Fe2+、Mn2+和Co2+）来维持，而氧化还原惰性过渡金属离子（Zn2+）会抑制MomA的活性。MomA既不含黄素假基，也不需要烟酰胺辅助因子进行单加氧，这表明MomA作为cupin超家族的成员是一种新型的单加氧酶。与MomA的催化特性一致，与MomA氨基酸序列相似且含有cupin结构域的white - orfii也能催化THN的单氧作用。white - orfii位于链霉菌A3中用于灰色孢子色素生物合成的白色II型PKS基因簇中“最小PKS”基因的上游(2)，并且在各种链霉菌中II型多酮生物合成基因簇中存在许多white - orfii同源物。这些发现表明一类新的醌生成单加氧酶参与了II型和III型PKSs合成的芳香聚酮的修饰。
RppA is a type III polyketide synthase (PKS) that catalyzes condensation of five molecules of malonyl-CoA to form 1,3,6,8-tetrahydroxynaphthalene (THN). In Streptomyces antibioticus IFO13271 and several other Streptomyces species, an open reading frame, named momA, is present as a neighbor of rppA. MomA belonged to the "cupin" superfamily because it contained a set of two motifs that is responsible for binding one equivalent of metal ions. MomA catalyzed monooxygenation of the THN produced from malonyl-CoA by the action of RppA to form flaviolin. In addition, it used several polyketides as substrates and formed the corresponding quinones. MomA required redox-active transition metal ions (Ni2+, Cu2+, Fe3+, Fe2+, Mn2+, and Co2+) for its activity, whereas it was inhibited by a redox-inert transition metal ion (Zn2+). MomA neither possessed any flavin prosthetic group nor required nicotinamide cofactors for monooxygenation, which shows that MomA as a member of the cupin superfamily is a novel monooxygenase. Consistent with the catalytic property of MomA, WhiE-ORFII showing similarity in amino acid sequence to MomA and containing a cupin domain also catalyzed monooxygenation of THN. whiE-ORFII is located immediately upstream of the "minimal PKS" gene within the whiE type II PKS gene cluster for biosynthesis of a gray spore pigment in Streptomyces coelicolor A3(2), and a number of whiE-ORFII homologues are present in the biosynthetic gene cluster for polyketides of type II in various Streptomyces species. These findings show that a novel class of quinone-forming monooxygenases is involved in modification of aromatic polyketides synthesized by PKSs of types II and III.