Approach and Workflow

A combination of basic and applied research, a translational scope with focus on entrepreneurship and a modern workflow makes the Center unique in its approach to cell factory design and development.
Our approach

The Novo Nordisk Foundation Center for Biosustainability (DTU Biosustain) aims at developing new knowledge and technologies to help facilitate the transformation from the existing oil-based chemical industry to a more sustainable bio-based society, in which chemicals are produced biologically.

A central scientific discipline is metabolic engineering, which involves design and genetically reprogramming of the metabolic processes of microorganisms like bacteria, yeast, fungi and mammalian cells (CHO). Engineering enables the organisms to convert biomass into valuable chemicals, including pharmaceuticals and food ingredients.

Furthermore, we seek to increase the chemical diversity of products by harnessing genetic information from the 99.9 % of microbes that cannot be cultivated in a laboratory and using this information in model organisms.

The extensive chemical diversity found in the plant kingdom is integrated by dedicated research on plant biochemistry and genetics.

We also have great focus on building computer models, platforms and tools to aid the discovery of new interesting molecules.

This triumvirate of increased chemical diversity, in silico design, and an expanded cell factory portfolio defines the next generation of microbial cell factories, which will be instrumental in the transition to the bio-based society. 

Workflow: Design, build, test, learn

There are three key technological drivers that have changed microbial cell factory design over the past decade:

  1. Genome sequencing
  2. Gene manipulation systems 
  3. Genome-scale models

These drivers in addition to an assortment of molecular biology and automation tools form the basis for an iterative process consisting of four principal steps:

  1. Design by genetic manipulation of the organism 
  2. Build the system at identify the producers by phenotyping 
  3. Test the cell by generating ‘omics’ data 
  4. Learn by mapping onto genome-scale models for analysis and decision making

If necessary, repeat the cycle.

This closed loop design process requires an integration of a suite of experimental and computational methods; a suite that needs to be continually developed and implemented. 
This iterative process represents the core paradigm and the organizational principle of the CFB; namely the design, construction and optimization of production strains. 

The inputs into the iterative design loop are compounds and their pathways in addition to the platform strains into which the design is built.

 

http://www.biosustain.dtu.dk/Research/Approach-and-Workflow
19 JANUARY 2019