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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Availability of specific reductases controls the temporal activity of the cytochrome P450 complement of Streptomyces coelicolor A3(2)
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Availability of specific reductases controls the temporal activity of the cytochrome P450 complement of Streptomyces coelicolor A3(2)

机译：特定还原酶的可用性控制链霉菌A3（2）的细胞色素P450补体的时间活性

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摘要

The annotated genome of Streptomyces coelicolor A3(2) revealed 18 cytosolic cytochromes P450 (CYPs) with six ferredoxin (fdx) proteins and two soluble ferredoxin reductases (fpr), their putative electron transport proteins. mRNA expression was observed for all 18 CYPs throughout growth and secondary metabolism, from 3 h after spore germination, and all CYP proteins examined also were present. Expression of members of the fdx complement was detected from the same time point, yet both fpr were detected only at 12 h. Six-hour exposure to dimethylbenzanthracene and benzo[a]pyrene xenobiotics resulted in the absence of some CYP mRNAs and expression of a specific fpr, FR2. This finding and the expression pattern during growth suggested that CYP activity may be regulated by availability of specific reductases. To test this proposal, we expressed in Escherichia coli and purified to homogeneity five CYPs: CYP105D5 (involved in xenobiotic metabolism) and CYP154A1, CYP154C1, CYP158A1, and CYP158A2 (putatively involved in secondary metabolism). Also the two soluble fpr (FR2 and FR3) proposed to shuttle electrons by means of fdx were purified, and specific interactions were observed so that FR2 preferentially reduced CYP105D5 (>90% reduction) compared with the other CYPs (>20% reduction), whereas FR3 preferentially reduced the other CYPs (>85% reduction) compared with CYP105D5 (>10%). Furthermore FR2 was shown to efficiently bind CYP105D5 and drive benzo[a]pyrene hydroxylation in contrast to FR3. These data show that control of CYP activity in S. coelicolor A3(2) involves specific interactions with fpr and their availability during the life cycle and, after xenobiotic exposure, represents a unique mechanism for regulating CYP function.
机译：带注释的天蓝色链霉菌A3（2）的基因组显示18种胞质细胞色素P450（CYP）和6种铁氧还蛋白（fdx）蛋白和2种可溶性铁氧还蛋白还原酶（fpr），它们是推定的电子转运蛋白。从孢子萌发后3小时开始，在整个生长和次生代谢中观察到所有18种CYP的mRNA表达，并且还存在所有检查的CYP蛋白。从相同的时间点检测到fdx补体成员的表达，但两个fpr仅在12 h时被检测到。暴露于二甲基苯并蒽和苯并[a] x异生物素六小时导致缺乏某些CYP mRNA和特定fpr，FR2的表达。这一发现和生长过程中的表达模式提示CYP活性可能受特定还原酶的可用性调节。为了测试该建议，我们在大肠杆菌中表达并纯化了五个CYP，使其同质：CYP105D5（涉及异源生物代谢）和CYP154A1，CYP154C1，CYP158A1和CYP158A2（可能参与次级代谢）。还纯化了提议通过fdx穿梭电子的两种可溶性fpr（FR2和FR3），并观察到特定的相互作用，因此FR2与其他CYP相比优先还原CYP105D5（降低> 90％），相比于CYP105D5（> 10％），FR3优先降低了其他CYP（降低了> 85％）。此外，与FR3相比，FR2已显示可有效结合CYP105D5并驱动苯并[a] re羟基化。这些数据表明，控制链球菌A3（2）中的CYP活性涉及与fpr的特异性相互作用及其在生命周期中的可用性，并且在异源生物暴露后，代表了一种调节CYP功能的独特机制。

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