Assb17/DesignPath

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FindPath and RetroPath: Solutions for in silico design of metabolic pathways

A guided tutorial to pathway design by Pablo Carbonell and Stephanie Heux .

Engineering cell factories to efficiently synthesize novel therapeutics and biofuels from novel substrates involves the development of tools for guiding the biologist in selecting the best metabolic pathways to be introduced in the host microorganism and able to support the desired metabolic function. In this tutorial, we will learn how to use FindPath and RetroPath two complementary computational tools enabling the in silico design of metabolic pathways. FindPath uses a chemical reaction database to generate possible metabolic pathways and exploits constraint-based models to identify the most efficient synthetic pathway to achieve the conversion of one or more novel substrate into any host metabolite. Retropath uses a retrosynthesis based approach to generate all the candidate pathways leading to the production of the target chemical and rank them based on several factors such as host compatibility, cytotoxicity, enzyme efficiency, and estimated steady-state fluxes.

Participants in this tutorial will pick a substrate and a target molecule of interest, from which FindPath and RetroPath will generate the metabolic map containing heterologous biosynthetic routes to the host organism. We will analyze how to enumerate and rank them and, in particular, how to evaluate aspects influencing the efficiency of the pathway such as the expected yield from flux balance analysis or the toxicity of intermediates to the host organism.

Projects

  • Reaction enumeration for retrosynthesis.
  • Find all pathways from a chemical target to a host chassis.
  • Prioritize pathways based on toxicity of chemicals.
  • Model growth rates and maximum yield for engineered strains.
  • Design DNA parts and constructs.