Aspergillus westerdijkiae polyketide synthase gene "aoks1" is involved in the biosynthesis of ochratoxin A

Aspergillus westerdijkiae polyketide synthase gene "aoks1" is involved in the biosynthesis of ochratoxin A
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DOI:
10.1016/j.fgb.2008.09.015
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发表时间:
2009-01-01
影响因子:
3
通讯作者:
Lebrihi, Ahmed
Lebrihi, Ahmed
中科院分区:
生物学3区
文献类型:
--
作者:
Bacha, Nafees;Atoui, Ali;Lebrihi, Ahmed

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赭曲霉毒素A(OTA)是一种具有肾毒性、致畸性、免疫原性、肝毒性和致癌性的真菌毒素,由韦斯特地基曲霉(Aspergillus westerdijkiae)NRRL 3174产生。在此,我们描述了一个假定的OTA-聚酮合酶基因“aoks 1”,克隆使用基因步行的方法。预测的2kb克隆的氨基酸序列与A. terreus中的compactin生物合成基因“mlcA”和P. nordicum中的OTA生物合成基因“otapksPN”。基于反转录PCR和动力学次级代谢产物的生产研究,aoks 1的表达被发现与OTA的生物合成。此外,其中aoks 1基因被大肠杆菌潮霉素B磷酸转移酶基因失活的突变体丧失了产生OTA的能力,但仍产生蜜醛。据我们所知,这份报告描述了第一次表征的基因参与OTA生物合成,与信息mellein这是在文献中提出的是一个中间OTA。aoks 1可能是A. westerdijkiae NRRL 3174. (C)2008年爱思唯尔公司All rights reserved.
Ochratoxin A (OTA) is a potential nephrotoxic, teratogenic, immunogenic, hepatotoxic and carcinogenic mycotoxin, produced by Aspergillus westerdijkiae NRRL 3174. Herein we describe the characterization of a putative OTA-polyketide synthase gene "aoks1", cloned by using gene walking approach. The predicted amino acid sequence of the 2 kb clone display 34-60% similarities to different polyketide synthase genes including lovastatine biosynthesis gene "lovb" in A. terreus, compactin biosynthesis gene "mlcA" in Penicillium citrinum and OTA biosynthesis gene "otapksPN" in P. nordicum. Based on the reverse transcription PCR and kinetic secondary metabolites production studies, aoks1 expression was found to be associated with OTA biosynthesis. Further a mutant, in which the aoks1 gene was inactivated by Escherichia coli hygromycin B phosphotransferase gene, lost the capacity to produce OTA, but still producing mellein. To our knowledge this report describes for the first time characterization of a gene involved in OTA biosynthesis, with the information about mellein which was proposed in the literature to be an intermediate OTA. This study also suggests that aoks1 may be the second polyketide synthase gene required for OTA biosynthesis in A. westerdijkiae NRRL 3174. (C) 2008 Elsevier Inc. All rights reserved.