Juvvadi Praveen Rao, Chivukula Subramanyam
Department of Biotechnology, The University of Tokyo, 1-1-1 Yayoi, Tokyo 113-8657, Japan.
Curr Microbiol. 2006 Jun;52(6):493-6. doi: 10.1007/s00284-005-0389-z. Epub 2006 Apr 25.
The inhibition of aflatoxin production by trifluoperazine, an anticalmodulin (CaM) agent and the relevance of Ca(2+)/CaM-dependent phosphorylation and dephosphorylation during aflatoxin biosynthesis was previously reported. To identify proteins that may be regulated by CaM, an in silico analysis for putative CaM-binding domains (CaMBDs) in the aflatoxin-related proteins of Aspergillus parasiticus was performed using the CaM target database. Interestingly, the key regulators of aflatoxin biosynthesis such as AflR and AflJ contained predicted CaMBDs at their C-termini. Furthermore, potential phosphorylation sites for CaM-kinase II were present within these CaMBDs. In addition to other aflatoxin biosynthesis enzymes--such as Vbs, DmtA and OmtA, and the VeA protein (known to regulate the expression of AflJ and AflR)--also showed the presence of putative CaMBDs. Although the present report reaffirms earlier observations on CaM-mediated regulation of aflatoxin biosynthesis, it also opens new avenues for identifying the specific targets of CaM and elucidating the exact mechanism of initiation and regulation of aflatoxin biosynthesis.
先前已有报道称,抗钙调蛋白(CaM)药物三氟拉嗪可抑制黄曲霉毒素的产生,以及黄曲霉毒素生物合成过程中Ca(2+)/CaM依赖性磷酸化和去磷酸化的相关性。为了鉴定可能受CaM调节的蛋白质,利用CaM靶标数据库对寄生曲霉黄曲霉毒素相关蛋白中的假定钙调蛋白结合结构域(CaMBDs)进行了计算机分析。有趣的是,黄曲霉毒素生物合成的关键调节因子,如AflR和AflJ,在其C末端含有预测的CaMBDs。此外,这些CaMBDs中存在CaM激酶II的潜在磷酸化位点。除了其他黄曲霉毒素生物合成酶——如Vbs、DmtA和OmtA,以及VeA蛋白(已知可调节AflJ和AflR的表达)——也显示存在假定的CaMBDs。虽然本报告再次证实了早期关于CaM介导的黄曲霉毒素生物合成调节的观察结果,但它也为鉴定CaM的特定靶标以及阐明黄曲霉毒素生物合成起始和调节的确切机制开辟了新途径。