Improvement of foreign protein production in Aspergillus niger var. awamori by constitutive induction of the unfolded protein response

摘要

Unfolded protein response (UPR) denotes the upregulation of ER-resident chaperone and foldase genes and numerous other genes involved in secretory functions during the accumulation of unfolded proteins into the ER. Over-expression of individual foldases and chaperones has been used in attempts to improve protein production in different production systems. In this paper a novel strategy to improve foreign protein production is demonstrated. We show that the constitutive induction of the UPR pathway in Aspergillus niger var. awamori can be achieved by expressing the activated form of the transcription factor hacA. This induction enhances the production of Trametes versicolor laccase by up to seven-fold and bovine preprochymosin by up to 2.8-fold in this biotechnically important fungus. The regulatory range of UPR was studied by analyzing the mRNA levels of novel A. niger var. awamori genes involved in different secretory functions. This revealed both similarities and differences to corresponding studies in S. cerevisiae.