Actinoplanes sp. SE50/110 is the natural producer of the diabetes mellitus drug acarbose, which is highly produced during the growth phase and ceases during the stationary phase. In previous works, the growth-dependency of acarbose formation was assumed to be caused by a decreasing transcription of the acarbose biosynthesis genes during transition and stationary growth phase. In this study, transcriptomic data using RNA-seq and state-of-the-art proteomic data from seven time points of controlled bioreactor cultivations were used to analyze expression dynamics during growth of Actinoplanes sp. SE50/110. A hierarchical cluster analysis revealed co-regulated genes, which display similar transcription dynamics over the cultivation time. Aside from an expected metabolic switch from primary to secondary metabolism during transition phase, we observed a continuously decreasing transcript abundance of all acarbose biosynthetic genes from the early growth phase until stationary phase, with the strongest decrease for the monocistronically transcribed genes acbA, acbB, acbD and acbE. Our data confirm a similar trend for acb gene transcription and acarbose formation rate. Surprisingly, the proteome dynamics does not follow the respective transcription for all acb genes. This suggests different protein stabilities or post-transcriptional regulation of the Acb proteins, which in turn could indicate bottlenecks in the acarbose biosynthesis. Furthermore, several genes are co-expressed with the acb gene cluster over the course of the cultivation, including eleven transcriptional regulators (e.g. ACSP50_0424), two sigma factors (ACSP50_0644, ACSP50_6006) and further genes, which have not previously been in focus of acarbose research in Actinoplanes sp. SE50/110. In conclusion, we have demonstrated, that a genome wide transcriptome and proteome analysis in a high temporal resolution is well suited to study the acarbose biosynthesis and the transcriptional and post-transcriptional regulation thereof.

中文翻译：

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阿卡波糖生物合成基因簇在Actinoplanes sp。中的表达。SE50 / 110取决于生长期

放线飞机sp。SE50 / 110是糖尿病药物阿卡波糖的天然生产者，阿卡波糖在生长期高产，在稳定期停止。在以前的工作中，阿卡波糖形成的生长依赖性被认为是由于在过渡和静止生长阶段阿卡波糖生物合成基因的转录减少引起的。在这项研究中，使用RNA-seq的转录组数据和来自受控生物反应器培养的七个时间点的最新蛋白质组学数据，来分析放线放线菌生长期间的表达动态。SE50 / 110。层次聚类分析揭示了共同调控的基因，这些基因在整个培养时间内显示出相似的转录动态。除了在过渡阶段预期的新陈代谢从一级代谢转变为二级代谢外，我们观察到从早期生长阶段到稳定期，所有阿卡波糖生物合成基因的转录本丰度持续下降，单顺反转录基因acbA，acbB，acbD和acbE的下降幅度最大。我们的数据证实了acb基因转录和阿卡波糖形成速率的相似趋势。出人意料的是，蛋白质组动力学并不遵循所有acb基因的各自转录。这表明Acb蛋白具有不同的蛋白稳定性或转录后调控，这反过来可能表明阿卡波糖生物合成的瓶颈。此外，在整个培养过程中，有几个基因与acb基因簇共表达，包括十一个转录调节因子（例如ACSP50_0424），两个σ因子（ACSP50_0644，ACSP50_6006）和其他基因，以前尚未在Actinoplanes sp。中进行阿卡波糖研究的重点。SE50 / 110。总而言之，我们已经证明，以高的时间分辨率进行全基因组的转录组和蛋白质组分析非常适合研究阿卡波糖的生物合成及其转录和转录后调控。