ValC，一种参与抗真菌剂井冈霉素A生物合成的新型C7-环醇激酶。
ValC, a new type of C7-Cyclitol kinase involved in the biosynthesis of the antifungal agent validamycin A.
作者信息
Minagawa Kazuyuki, Zhang Yirong, Ito Takuya, Bai Linquan, Deng Zixin, Mahmud Taifo
机构信息
Department of Pharmaceutical Sciences, Oregon State University, Corvallis, OR 97331-3507, USA.
出版信息
Chembiochem. 2007 Apr 16;8(6):632-41. doi: 10.1002/cbic.200600528.
Abstract
The gene valC, which encodes an enzyme homologous to the 2-epi-5-epi-valiolone kinase (AcbM) of the acarbose biosynthetic pathway, was identified in the validamycin A biosynthetic gene cluster. Inactivation of valC resulted in mutants that lack the ability to produce validamycin A. Complementation experiments with a replicating plasmid harboring full-length valC restored the production of validamycin A, thus suggesting a critical function of valC in validamycin biosynthesis. In vitro characterization of ValC revealed a new type of C7-cyclitol kinase, which phosphorylates valienone and validone--but not 2-epi-5-epi-valiolone, 5-epi-valiolone, or glucose--to afford their 7-phosphate derivatives. The results provide new insights into the activity of this enzyme and also confirm the existence of two different pathways leading to the same end-product: the valienamine moiety common to acarbose and validamycin A.
摘要
在井冈霉素A生物合成基因簇中鉴定出了基因valC，该基因编码一种与阿卡波糖生物合成途径中的2-表-5-表-缬草酮激酶（AcbM）同源的酶。valC的失活导致突变体丧失产生井冈霉素A的能力。用携带全长valC的复制质粒进行的互补实验恢复了井冈霉素A的产生，这表明valC在井冈霉素生物合成中具有关键作用。对ValC的体外特性分析揭示了一种新型的C7-环醇激酶，该酶可将井冈烯胺和井冈霉素酮磷酸化——但不能将2-表-5-表-缬草酮、5-表-缬草酮或葡萄糖磷酸化——以生成它们的7-磷酸衍生物。这些结果为该酶的活性提供了新的见解，也证实了存在两条导致相同终产物的不同途径：阿卡波糖和井冈霉素A共有的井冈胺部分。
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