Genetic manipulation of transcription factors involved in the secretion of recombinant enzymes in Aspergillus nidulans

• Grant number: 20/15962-6
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: April 01, 2022
• End date: August 31, 2025
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: André Ricardo de Lima Damasio
• Grantee: Everton Paschoal Antoniel
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated scholarship(s): 23/07394-6 - Engineering transcription factors to optimize recombinant protein production in filamentous fungi, BE.EP.DR

Abstract

Filamentous fungi are capable of secreting a large amount of proteins and are used as a platform for the production of industrially relevant enzymes. However, levels of recombinant protein production still need to be improved. In this regard, many strategies have been applied to improve its production capacity, nevertheless, as there is an increase in market demand and productivity is still relatively low, identifying new genetic targets to promote the increase in enzyme secretion is becoming more and more important. Therefore, the main goal of this project is to evaluate the production/secretion of a recombinant enzyme in strains of Aspergillus nidulans in which target transcription factors have been genetically manipulated (deleted and/or overexpressed). The transcription factors to be manipulated were selected from RNA-seq data from A. nidulans strains overexpressing three heterologous enzymes. These RNA-seq data analyzes, added to a protease secretion assay, demonstrated that these transcription factors are possibly involved in different biological processes related to the protein secretion pathway. Therefore, this study aims to find transcription factors involved in the production/secretion of recombinant proteins in A. nidulans, and to engineer mutant strains with improved production of recombinant enzymes of biotechnological interest. Additionally, we intend to describe the mechanisms involved in this increase in production. In conclusion, these goals may provide researchers with resources to better propose rational engineering strategies that improve the secretion process in filamentous fungi. (AU)