An in silico platform for the design of heterologous pathways in nonnative metabolite production

Sunisa Chatsurachai,Hiroshi Shimizu,Chikara Furusawa

doi:10.1186/1471-2105-13-93

Abstract

BackgroundMicroorganisms are used as cell factories to produce valuable compounds in pharmaceuticals, biofuels, and other industrial processes. Incorporating heterologous metabolic pathways into well-characterized hosts is a major strategy for obtaining these target metabolites and improving productivity. However, selecting appropriate heterologous metabolic pathways for a host microorganism remains difficult owing to the complexity of metabolic networks. Hence, metabolic network design could benefit greatly from the availability of an in silico platform for heterologous pathway searching.ResultsWe developed an algorithm for finding feasible heterologous pathways by which nonnative target metabolites are produced by host microorganisms, using Escherichia coli, Corynebacterium glutamicum, and Saccharomyces cerevisiae as templates. Using this algorithm, we screened heterologous pathways for the production of all possible nonnative target metabolites contained within databases. We then assessed the feasibility of the target productions using flux balance analysis, by which we could identify target metabolites associated with maximum cellular growth rate.ConclusionsThis in silico platform, designed for targeted searching of heterologous metabolic reactions, provides essential information for cell factory improvement.

Highlights

Microorganisms are used as cell factories to produce valuable compounds in pharmaceuticals, biofuels, and other industrial processes
Ethanol and higher alcohols are used as fuels and solvents in a wide variety of chemical processes [7]. 1,3-propanediol forms the basis of polymers such as polytrimethylene terephthalate (PTT) [8], while isoprene is an intermediate metabolite in the production of cis-1,4-polyisoprene, a synthetic of natural rubber [9]
Heterologous reaction screening generally requires extensive calculations; it is difficult to compare the screening results. To avoid such calculations, we developed a simple in silico screening platform to identify feasible heterologous pathways of nonnative target metabolite production

Summary

Introduction

Microorganisms are used as cell factories to produce valuable compounds in pharmaceuticals, biofuels, and other industrial processes. 1,3-propanediol forms the basis of polymers such as polytrimethylene terephthalate (PTT) [8], while isoprene is an intermediate metabolite in the production of cis-1,4-polyisoprene, a synthetic of natural rubber [9] To produce such industrially useful materials, modifications of host metabolic systems are generally required. Several in silico heterologous pathway search methods have been proposed and used in target metabolite production [19,20,21,22,23,24,25,26,27,28,29,30] Some of these predict metabolic pathways based on chemical transformation patterns between the substrate and the product [19,20,24,25]. By supplying information about reactions, PathPred enables the user to create a metabolite that is structurally similar to the target

Methods

Results

Conclusion