Scaffoldomics for product yield maximization of fine chemicals in microbial cell factories

01 November 2021 → 31 October 2025
Research Foundation - Flanders (FWO)
Research disciplines
  • Engineering and technology
    • Biocatalysis and enzyme technology
    • Bioprocessing, bioproduction and bioproducts
    • Fermentation
    • Industrial molecular engineering of nucleic acids and proteins
Bio-based fermentation of fine chemicals Colocalization of biosynthetic pathways Plant flavonoids
Project description

A main challenge for the future economy is the transition from an oil-based to a bio-based industry. This transition requires the development of cost competitive production processes starting from renewable resources. Insufficient product yield is often a killer for new microbial cell factories developed for the production of fine chemicals. Consequently, a massive amount of time and efforts are invested in yield maximization. Colocalization of the enzymes of a biosynthetic pathway for the production of fine chemicals is a proven approach to multiply the product yield. Indeed, enzyme proximity promotes channeling of intermediates from one enzyme to the other, called ‘substrate channeling’. Colocalization can be achieved by docking the enzymes onto a common protein scaffold. Enzymes are then recruited to the scaffold by fusing them to domains that bind to their interaction partner domains in the scaffold. However, the current procedures for scaffolding are cumbersome and time-consuming. In this project, I will develop the ‘scaffoldomics’ platform. I will build a generic synthetic framework for combinatorial scaffolding of biosynthetic pathways for the rapid identification of the best scaffolded pathway. Scaffoldomics will be driven by a new DNA assembly method (VersaTile; WO 2018/114980). In this project, I will elaborate the platform for a maximized production of naringenin and luteolin. Both fine chemicals belong to the plant flavonoids and have a multitude of applications.