Construction of a Metabolic Model of Aspergillus oryzae: Guiding the production of recombinant proteins by Precision Fermentation

• Grant number: 25/01711-5
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: April 01, 2025
• End date: May 31, 2028
• Field of knowledge: Biological Sciences - Biochemistry - Biochemistry of Microorganisms
• Principal Investigator: André Ricardo de Lima Damasio
• Grantee: Bruno Batista
• 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

Given the growing environmental concerns, it is essential to seek alternatives to current production models. Precision fermentation emerges as a promising solution, utilizing natural resources to produce a variety of compounds, including proteins. Filamentous fungi, such as Aspergillus oryzae, are natural biofactories that, through genetic engineering, can be optimized to produce various recombinant proteins. However, the genetic manipulation of these organisms presents significant challenges that need to be overcome. For this reason, the application of metabolic models can greatly accelerate the development and guidance of strain design strategies. Advances in bioinformatics, combined with omics techniques, create a favorable scenario for the development of integrative models that simulate organisms in silico, potentially revealing bottlenecks in protein expression. This work aims to develop an integrative metabolic model of A. oryzae in the context of precision fermentation for the production of heterologous proteins, using transcriptomic, proteomic, and thermodynamic data. Additionally, it seeks to identify critical bottlenecks for the construction of a superproductive protein chassis strain through metabolic engineering.