Workshop 1: Tools for Commercial Bioprocess Design, Economic Analysis, and Scale-up
Want to produce large volume intermediate or specialty chemicals? This workshop will expose you to a better way to design commercially relevant high-yield bioprocesses.
This workshop will cover: 1) technoeconomic analysis methods; 2) approaches to rapidly debottleneck and improve production organisms; 3) scale down strategies to improve scale up and 4) real-world commercial case studies. Finally, we’ll describe ways to reduce the time, cost and technical risk of process development to increase the rate of adoption.
Our workshop begins by challenging the traditional wisdom of an “organism-first” approach. We “begin with the end in mind,” from a “process-first” point of view. That drives the prime importance of starting with techno-economic analysis (TEA) and continuing to apply it throughout the entire development cycle. This requires the parallel optimization of the organism, the fermentation process, and downstream product recovery.
As the design of an integrated process evolves, the metabolic bottlenecks in the organism can shift. These challenges are addressed with an iterative and integrative approach that combines large-scale generation and analysis of heterogeneous data types across multiple scales (well-plates to lab-scale & industrial-scale bioreactors) and the application of systems bioengineering and predictive small-scale platforms to design strains that optimize metabolism and product yield under conditions compatible with at-scale constraints.
Regarding process development, we’ll show how scaling down is a great way to scale up faster and at lower cost. Similarly, we will teach how to “push” the system to make it robust under the kinds of process upsets that happen in real plants.
Workshop 2: Modelling Concepts in Metabolic Engineering
The rapid influx of omics data and automated annotation pipelines has enabled the rapid construction of organism-specific (and even community level) metabolic models. The quality and scope of these models is increasingly improving through the expanding access to metabolite and reaction databases, thermodynamic data, kinetic information, enzyme localization, transporter data, and sophisticated curation and correction algorithms. Using this modeling infrastructure, algorithmic contributions are homing in on the prediction of genetic intervention strategies in strain design, assembly of complex pathways towards targeted products, elucidation of genome-wide metabolic flux distributions given 13C data and tracking of both small molecules and macromolecules in metabolism. In this workshop, we will provide an overview of some of these advances and then proceed with three tutorials on: (i) “KBase: a web-platform for collaborative assembly, annotation, and modeling of genomic and metagenomic data” by Dr. Chris Henry, ANL; (ii) “Metabolic modeling and computer-aided strain design using cobrapy, cameo, memote and DD-DeCaF” by Dr. Niko Sonnenschein, DTU Biosustain; and (iii) “Web-based tools for metabolic network analysis: Thermodynamic profiling and enzyme-cost minimization” by Dr. Elad Noor, ETH.