Department of Biotechnology and Food Microbiology, Poznan University of Life Sciences, Wojska Polskiego 48, 60-637 Poznan, Poland.
Int J Mol Sci. 2024 Aug 30;25(17):9450. doi: 10.3390/ijms25179450.
Transcriptional regulatory networks (TRNs) associated with recombinant protein (rProt) synthesis in are still under-described. Yet, it is foreseen that skillful manipulation with TRNs would enable global fine-tuning of the host strain's metabolism towards a high-level-producing phenotype. Our previous studies investigated the transcriptomes of strains overproducing biochemically different rProts and the functional impact of transcription factors (TFs) overexpression (OE) on rProt synthesis capacity in this species. Hence, much knowledge has been accumulated and deposited in public repositories. In this study, we combined both biological datasets and enriched them with further experimental data to investigate an interplay between TFs and rProts synthesis in at transcriptional and functional levels. Technically, the RNAseq datasets were extracted and re-analyzed for the TFs' expression profiles. Of the 140 TFs in , 87 TF-encoding genes were significantly deregulated in at least one of the strains. The expression profiles were juxtaposed against the rProt amounts from 125 strains co-overexpressing TF and rProt. In addition, several strains bearing knock-outs (KOs) in the TF loci were analyzed to get more insight into their actual involvement in rProt synthesis. Different profiles of the TFs' transcriptional deregulation and the impact of their OE or KO on rProts synthesis were observed, and new engineering targets were pointed.
在 中与重组蛋白 (rProt) 合成相关的转录调控网络 (TRNs) 仍未得到充分描述。然而，可以预见的是，熟练地操纵 TRNs 将使宿主菌株的代谢能够进行全局精细调控，以达到高产表型。我们之前的研究调查了过度表达生化性质不同 rProt 的 菌株的转录组，以及转录因子 (TFs) 过表达 (OE) 对该物种中 rProt 合成能力的功能影响。因此，已经积累了大量的知识并存储在公共存储库中。在这项研究中，我们将两个生物数据集结合起来，并通过进一步的实验数据进行了丰富，以在转录和功能水平上研究 TF 和 rProt 在 中的相互作用。从技术上讲，我们提取了 RNAseq 数据集并重新分析了 TF 的表达谱。在 中的 140 个 TF 中，至少有 87 个 TF 编码基因在至少一种菌株中显著失调。将表达谱与 125 株共过表达 TF 和 rProt 的菌株中的 rProt 量进行了对比。此外，还分析了几个 TF 基因座发生敲除 (KO) 的菌株，以更深入地了解它们在 rProt 合成中的实际参与情况。观察到 TF 转录失调的不同模式，以及它们的 OE 或 KO 对 rProt 合成的影响，并指出了新的工程靶点。
