期刊
ACS SYNTHETIC BIOLOGY
卷 7, 期 8, 页码 1858-1873出版社
AMER CHEMICAL SOC
DOI: 10.1021/acssynbio.8b00049
关键词
novel synthetic pathways; pathway feasibility; pathway similarity; methyl ethyl ketone; 2-butanone; E. coli
资金
- Ecole Polytechnique Federale de Lausanne (EPFL)
- SynPath project through ERA-SynBio Initiative for the robust development of Synthetic Biology [ERASYNBIO1-016]
- RTD grant MicroScapesX within SystemX [2013/158]
- Swiss Initiative for System Biology
- German Federal Ministry of Education and Research [031A459]
The limited supply of fossil fuels and the establishment of new environmental policies shifted research in industry and academia toward sustainable production of the second generation of biofuels, with methyl ethyl ketone (MEK) being one promising fuel candidate. MEK is a commercially valuable petrochemical with an extensive application as a solvent. However, as of today, a sustainable and economically viable production of MEK has not yet been achieved despite several attempts of introducing biosynthetic pathways in industrial microorganisms. We used BNICE.ch as a retrobiosynthesis tool to discover all novel pathways around MEK. Out of 1325 identified compounds connecting to MEK with one reaction step, we selected 3-oxopentanoate, but-3-en-2-one, but-1-en-2-olate, butylamine, and 2-hydroxy-2-methylbutanenitrile for further study. We reconstructed 3 679 610 novel biosynthetic pathways toward these 5 compounds. We then embedded these pathways into the genome-scale model of E. coli, and a set of 18 622 were found to be the most biologically feasible ones on the basis of thermodynamics and their yields. For each novel reaction in the viable pathways, we proposed the most similar KEGG reactions, with their gene and protein sequences, as candidates for either a direct experimental implementation or as a basis for enzyme engineering. Through pathway similarity analysis we classified the pathways and identified the enzymes and precursors that were indispensable for the production of the target molecules. These retrobiosynthesis studies demonstrate the potential of BNICE.ch for discovery, systematic evaluation, and analysis of novel pathways in synthetic biology and metabolic engineering studies.
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