Multiplex deletion of secreted proteins in Aspergillus oryzae: a minimum secretome

• Grant number: 23/12218-2
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: November 01, 2023
• End date: October 31, 2025
• Field of knowledge: Biological Sciences - Biochemistry - Biochemistry of Microorganisms
• Principal Investigator: André Ricardo de Lima Damasio
• Grantee: Lana Ohara Souza Silva
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 22/05731-2 - BEYOND: establishing a fungal cell factory for recombinant protein production, AP.TEM

Abstract

Filamentous fungi, such as Aspergillus sp. and Trichoderma sp., can produce and secrete a variety of enzymes, making them the primary cellular factories for industrial enzyme production. Despite A. oryzae being used as a cellular factory, the efficient production of recombinant proteins in this specie still faces challenges, including transcription, translation, protein folding, post-translational modifications, transport, and secretion, which have led to limited production titers. It is known that the overproduction of recombinant proteins in Aspergillus strains triggers the unfolded protein response (UPR), mediated by the action of the transcription factor HacA, which induces target genes in this response. Additionally, it leads to the induction of a mechanism called repression under secretion stress (RESS), which mitigates endoplasmic reticulum overload, promoting cellular homeostasis. Proteomic analyses of recombinant A. nidulans strains reveal the enrichment of various biological processes, including energy pathways, amino acid metabolism, protein synthesis, oxidative stress, and endoplasmic reticulum stress. Several omics studies related to stress response and protein processing in the endoplasmic reticulum in A. oryzae indicate differentially expressed genes common to these processes. This information is of paramount importance and should be taken into consideration in the process of optimizing the production of recombinant proteins in filamentous fungi, such as A. oryzae.