MARSI: metabolite analogues for rational strain improvement

João G. R. Cardoso; Ahmad A Zeidan; Kristian Jensen; Nikolaus Sonnenschein; Ana Rute Neves; Markus J Herrgård

doi:10.1093/bioinformatics/bty108

MARSI: metabolite analogues for rational strain improvement

João G. R. Cardoso, Ahmad A Zeidan, Kristian Jensen, Nikolaus Sonnenschein, Ana Rute Neves, Markus J Herrgård^*

^*Corresponding author for this work

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Abstract

Metabolite analogues (MAs) mimic the structure of native metabolites, can competitively inhibit their utilization in enzymatic reactions, and are commonly used as selection tools for isolating desirable mutants of industrial microorganisms. Genome-scale metabolic models representing all biochemical reactions in an organism can be used to predict effects of MAs on cellular phenotypes. Here, we present the Metabolite Analogues for Rational Strain Improvement (MARSI) framework. MARSI provides a rational approach to strain improvement by searching for metabolites as targets instead of genes or reactions. The designs found by MARSI can be implemented by supplying MAs in the culture media, enabling metabolic rewiring without the use of recombinant DNA technologies that cannot always be used due to regulations. To facilitate experimental implementation, MARSI provides tools to identify candidate MAs to a target metabolite from a database of known drugs and analogues.

Original language	English
Journal	Bioinformatics
Volume	34
Issue number	13
Pages (from-to)	2319-2321
ISSN	1367-4803
DOIs	https://doi.org/10.1093/bioinformatics/bty108
Publication status	Published - 2018

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This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

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abstract = "Metabolite analogues (MAs) mimic the structure of native metabolites, can competitively inhibit their utilization in enzymatic reactions, and are commonly used as selection tools for isolating desirable mutants of industrial microorganisms. Genome-scale metabolic models representing all biochemical reactions in an organism can be used to predict effects of MAs on cellular phenotypes. Here, we present the Metabolite Analogues for Rational Strain Improvement (MARSI) framework. MARSI provides a rational approach to strain improvement by searching for metabolites as targets instead of genes or reactions. The designs found by MARSI can be implemented by supplying MAs in the culture media, enabling metabolic rewiring without the use of recombinant DNA technologies that cannot always be used due to regulations. To facilitate experimental implementation, MARSI provides tools to identify candidate MAs to a target metabolite from a database of known drugs and analogues.",

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AU - Herrgård, Markus J

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MARSI: metabolite analogues for rational strain improvement

Abstract

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