文献类型：期刊文献

英文题名：Transcriptome analysis reveals methanol metabolism variations for the growth damage caused by overexpression of chimeric transactivators in Pichia pastoris

作者：Liu, Qi[1];He, Ziyu[1];Cai, Menghao[1,2]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, 130 Meilong Rd, Shanghai 200237, Peoples R China;[2]Shanghai Collaborat Innovat Ctr Biomfg, Shanghai 200237, Peoples R China

年份：2025

卷号：10

期号：1

起止页码：133

外文期刊名：SYNTHETIC AND SYSTEMS BIOTECHNOLOGY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001359067000001)】；

基金：This study was supported by National Key Research and Develop-ment Program of China (2022YFC2805102) , Young Scientist Fund of National Natural Science Foundation of China (32201206) , and China Postdoctoral Science Foundation (2022M711146) . We are grateful for the sequencing platform and bioinformation analysis of Gene Denovo Biotechnology Co., Ltd (Guangzhou, China) .

语种：英文

外文关键词：Pichia pastoris; Methanol metabolism; Transcriptome analysis; Transcription activator; AOX1 promoter

摘要：Methanol is a promising substrate for sustainable biomanufacturing, and Pichia pastoris has become a commonly used yeast for methanol utilization due to its powerful methanol metabolic pathways and methanol inducible promoter. Previous reconstruction of gene circuits highly improved transcriptional activity, but excessive expression of chimeric transactivator damaged cell growth on methanol. Here we employed transcriptome analysis to investigate the effects of chimeric transactivator overexpression on cellular metabolism and regulatory networks. The results showed that strong expression of chimeric transactivator unexpectedly downregulated methanol metabolism, especially the alcohol oxidase 1 (AOX1), but without remarkable changes in expression of transcriptional factors. Meanwhile, the synthesis of peroxisomes also varied with chimeric transactivator expression. In addition, the enrichment analysis of differentially expressed genes revealed their impact on cellular metabolism. The gene expression patterns caused by different expression levels of chimeric trans- activators have also been clarified. This work provides useful information to understand the transcriptional regulation of the AOX1 promoter and methanol signaling. It revealed the importance of balancing transcription factor expression for the host improvement.