Cryptosporidium parvum: the first protist known to encode a putative polyketide synthase.
Cryptosporidium parvum: the first protist known to encode a putative polyketide synthase.
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小隐孢子虫：已知的第一个编码假定的聚酮合酶的原生生物。
DOI：
10.1016/s0378-1119(02)00931-9
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发表时间：
2002
期刊：
影响因子：
3.5
通讯作者：
Keithly,JanetS
中科院分区：
文献类型：
--
作者：
Zhu,Guan;LaGier,MichaelJ;Stejskal,Frantisek;Millership,JasonJ;Cai,Xiaomin;Keithly,JanetS
我们报告了一个假定的多功能I型聚酮合酶（PKS）基因从顶复形隐孢子虫（CpPKS 1）。40 kb的无内含子开放阅读框（ORF）预测了13，414个氨基酸的单一多肽，分子量为1516.5 kDa。序列分析确定了该蛋白中至少29个酶结构域。这些结构域被组织成一个N-末端装载单元，七个聚酮链延伸模块，和一个羧基终止子单元。加载结构域由酰基辅酶A连接酶（AL）和酰基载体蛋白（ACP）组成。所有七个延伸模块含有延伸两碳（C2）酰基单元所需的六个结构域中的两个至五个，即酮脂酰合酶、酰基转移酶、脱氢酶、烯酰还原酶、酮还原酶和/或ACP。羧基终止子与各种还原酶同源，表明最终的延长产物不是如在大多数I型PKS和所有脂肪酸合成酶（FAS）系统中观察到的由硫酯酶水解释放，而是通过还原反应释放，这已经在一些非核糖体肽合成酶系统中得到证实。CpPKS 1蛋白质序列和结构域结构类似于先前报道的C. parvum脂肪酸合成酶（CpFAS 1），由25 kb ORF编码。C. PKS/FAS中酰基转移酶的最大似然系统发育分析parvum和其他生物体清楚地区分了乙酸盐延伸的进化枝与那些结合丙酸盐的进化枝。所有来自CpPKS 1和先前报道的CpFAS 1的酰基转移酶结构域都聚集在乙酸延伸基团内，这表明只有非甲基化的C2单元才被C.小聚酮和脂肪酸脱氢酶。通过逆转录-聚合酶链反应和免疫荧光显微镜证实CpPKS 1的表达。许多聚酮化合物是医学上重要的抗生素、抗癌剂、毒素或信号分子。因此，推测CpPKS 1在这种顶复体和艾滋病患者这种机会性感染引起的疾病中可能发挥什么作用是有趣的。
We are reporting a putative multifunctional Type I polyketide synthase (PKS) gene from the apicomplexan Cryptosporidiumparvum (CpPKS1). The 40 kb intronless open reading frame (ORF) predicts a single polypeptide of 13,414 amino acids with a molecular mass of 1516.5 kDa. Sequence analysis identified at least 29 enzymatic domains within this protein. These domains are organized into an N-terminal loading unit, seven polyketide chain elongation modules, and a carboxy terminator unit. The loading domain consists of an acyl-CoA ligase (AL) and an acyl carrier protein (ACP). All seven elongation modules contain between two and five of the six domains required for the elongation of two-carbon (C2) acyl units, i.e. ketoacyl synthase, acyl transferase, dehydrase, enoyl reductase, ketoreductase and/or ACP. The carboxy terminator is homologous to various reductases, suggesting that the final elongated product is not hydrolytically released by thioesterases as observed in most Type I PKS and all fatty acid synthetase (FAS) systems, but by a reducing reaction, which has been demonstrated in some non-ribosomal peptide synthase systems. The protein sequence and domain organization of CpPKS1 protein resembles a previously reported C. parvum fatty acid synthase (CpFAS1), which is encoded by a 25 kb ORF. Maximum likelihood phylogenetic analysis of acyl transferases within PKS/FAS from C. parvum and other organisms clearly differentiates acetate-extending clades from those incorporating propionate. All acyl transferase domains from CpPKS1, and a previously reported CpFAS1, clustered within the acetate-extending group, suggesting the likelihood that only non-methylated C2 units are incorporated by C. parvum polyketide and fatty acid synthases. The expression of CpPKS1 was confirmed by reverse transcription-polymerase chain reaction and immunofluorescence microscopy. Many polyketides are medically significant antibiotics, anticancer agents, toxins, or signaling molecules. Therefore, it is interesting to speculate what role CpPKS1 might play in this apicomplexan and the disease caused by this opportunistic infection of AIDS patients.