Exploring De Novo metabolic pathways from pyruvate to propionic acid
Andrew Stine1, Miaomin Zhang1, Soo Ro1
1Dept. of Chemical and Biological Engineering, Northwestern University, Evanston, IL.
Biotechnology Progress
|January 30, 2016
Summary
Computational tools like BNICE can design novel biochemical pathways for sustainable chemical production. This study used BNICE to find new routes for propionic acid synthesis, avoiding unwanted byproducts and identifying new enzyme functions.
Area of Science:
- Industrial biotechnology
- Metabolic engineering
- Synthetic biology
Background:
- Industrial biotechnology offers sustainable chemical production, but pathway design is limited by known reactions.
- Enzyme promiscuity allows novel reactions, expanding the potential of biochemical pathway design.
- Existing propionic acid pathways yield undesirable byproducts, reducing economic viability.
Purpose of the Study:
- To design novel biochemical pathways for propionic acid synthesis from pyruvate using computational methods.
- To identify pathways that avoid common byproducts like lactic and succinic acid.
- To computationally predict and experimentally validate novel enzyme activities for industrial applications.
Main Methods:
- Utilized the Biological Network Integrated Computational Explorer (BNICE) program to predict enzyme activities and design synthetic pathways.
- Employed generalized reaction rules from biochemical databases to guide pathway prediction.
- Focused on the reduction of acrylic acid to propionic acid, experimentally validating enzyme function.
Main Results:
- BNICE predicted seven efficient propionic acid synthesis pathways, with five avoiding undesirable byproducts.
- Over 28% of the reactions in the designed pathways involved novel enzyme substrates not in the BNICE training set.
- Oye2p from Saccharomyces cerevisiae was experimentally validated to catalyze the reduction of acrylic acid to propionic acid.
Conclusions:
- BNICE is a valuable tool for discovering novel biochemical pathways and predicting enzyme promiscuity.
- Computational methods can identify new enzymatic reactions for industrial applications, such as propionic acid production.
- The findings support the use of enzyme promiscuity in metabolic engineering for improved chemical synthesis.
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