Correlation of gene expression and protein production rate - a system wide study

BMC Genomics

Research Article

Bart Smit¹  Jari Rautio²  Erno Lindfors³  Markku Saloheimo³  Tiina Pakula³  Marilyn Wiebe³  Merja Penttilä³  Paula Jouhten³  Mikko Arvas³  Heini Koivistoinen⁴ 

[1] NIZO food research, Kernhemseweg 2, 6718ZB, Ede, The Netherlands;Plexpress, Viikinkaari 6, 00790, Helsinki, Finland;VTT Technical Research Centre of Finland, P.O. Box FI-1000, Tietotie 2, 02044 VTT, Espoo, Finland;Ypap Oy, Hyrsynkulmantie 68, FI-32100, Ypäjä, Finland;

关键词: Unfolded Protein Response;    High Cell Density;    Chemostat Cultivation;    High Cell Density Cultivation;    Lineage Specific Gene;   

DOI  :  10.1186/1471-2164-12-616

 received in 2011-08-25, accepted in 2011-12-20,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundGrowth rate is a major determinant of intracellular function. However its effects can only be properly dissected with technically demanding chemostat cultivations in which it can be controlled. Recent work on Saccharomyces cerevisiae chemostat cultivations provided the first analysis on genome wide effects of growth rate. In this work we study the filamentous fungus Trichoderma reesei (Hypocrea jecorina) that is an industrial protein production host known for its exceptional protein secretion capability. Interestingly, it exhibits a low growth rate protein production phenotype.ResultsWe have used transcriptomics and proteomics to study the effect of growth rate and cell density on protein production in chemostat cultivations of T. reesei. Use of chemostat allowed control of growth rate and exact estimation of the extracellular specific protein production rate (SPPR). We find that major biosynthetic activities are all negatively correlated with SPPR. We also find that expression of many genes of secreted proteins and secondary metabolism, as well as various lineage specific, mostly unknown genes are positively correlated with SPPR. Finally, we enumerate possible regulators and regulatory mechanisms, arising from the data, for this response.ConclusionsBased on these results it appears that in low growth rate protein production energy is very efficiently used primarly for protein production. Also, we propose that flux through early glycolysis or the TCA cycle is a more fundamental determining factor than growth rate for low growth rate protein production and we propose a novel eukaryotic response to this i.e. the lineage specific response (LSR).

【 授权许可】

CC BY   
© Arvas et al; licensee BioMed Central Ltd. 2011