Computational pathway design tools often face the challenges of balancing the stoichiometry of co-metabolites and cofactors, and dealing with reaction rule utilization in a single workflow. To this end, we provide an overview of two complementary stoichiometry-based pathway design tools optStoic and novoStoic developed in our group to tackle these challenges. optStoic is designed to determine the stoichiometry of overall conversion first which optimizes a performance criterion (e.g. high carbon/energy efficiency) and ensures a comprehensive search of co-metabolites and cofactors. The procedure then identifies the minimum number of intervening reactions to connect the source and sink metabolites. We also further the pathway design procedure by expanding the search space to include both known and hypothetical reactions, represented by reaction rules, in a new tool termed novoStoic. Reaction rules are derived based on a mixed-integer linear programming (MILP) compatible reaction operator, which allow us to explore natural promiscuous enzymes, engineer candidate enzymes that are not already promiscuous as well as design de novo enzymes. The identified biochemical reaction rules then guide novoStoic to design routes that expand the currently known biotransformation space using a single MILP modeling procedure. We demonstrate the use of the two computational tools in pathway elucidation by designing novel synthetic routes for isobutanol.
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June 2018
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Review Article|
April 06 2018
Exploring the combinatorial space of complete pathways to chemicals
Lin Wang;
Lin Wang
1Department of Chemical Engineering, The Pennsylvania State University, University Park, State College, PA 16802, U.S.A.
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Chiam Yu Ng;
Chiam Yu Ng
1Department of Chemical Engineering, The Pennsylvania State University, University Park, State College, PA 16802, U.S.A.
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Satyakam Dash;
Satyakam Dash
1Department of Chemical Engineering, The Pennsylvania State University, University Park, State College, PA 16802, U.S.A.
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Costas D. Maranas
1Department of Chemical Engineering, The Pennsylvania State University, University Park, State College, PA 16802, U.S.A.
Correspondence: Costas D. Maranas ([email protected])
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Publisher: Portland Press Ltd
Received:
December 17 2017
Revision Received:
February 21 2018
Accepted:
February 26 2018
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2018
Biochem Soc Trans (2018) 46 (3): 513–522.
Article history
Received:
December 17 2017
Revision Received:
February 21 2018
Accepted:
February 26 2018
Citation
Lin Wang, Chiam Yu Ng, Satyakam Dash, Costas D. Maranas; Exploring the combinatorial space of complete pathways to chemicals. Biochem Soc Trans 19 June 2018; 46 (3): 513–522. doi: https://doi.org/10.1042/BST20170272
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