title: Metabolic anchor reactions for robust biorefining.
abstract: Microbial cell factories based on renewable carbon sources are fundamental to a sustainable bio-economy. The economic feasibility of producer cells requires robust performance balancing growth and production. However, the inherent competition between these two objectives often leads to instability and reduces productivity. While algorithms exist to design metabolic network reduction strategies for aligning these objectives, the biochemical basis of the growth-product coupling has remained unresolved. Here, we reveal key reactions in the cellular biochemical repertoire as universal anchor reactions for aligning cell growth and production. A necessary condition for a reaction to be an anchor is that it splits a substrate into two or more molecules. By searching the currently known biochemical reaction space, we identify 62 C-C cleaving anchor reactions, such as isocitrate lyase (EC 4.1.3.1) and L-tryptophan indole-lyase (EC 4.1.99.1), which are relevant for biorefining. The here identified anchor reactions mark network nodes for basing growth-coupled metabolic engineering and novel pathway designs.
authors.affiliation: European Molecular Biology Laboratory, Heidelberg, Germany.
authors.forename: Paula
authors.initials: P
authors.lastname: Jouhten
authors.affiliation: European Molecular Biology Laboratory, Heidelberg, Germany.
authors.forename: Jaime
authors.initials: J
authors.lastname: Huerta-Cepas
authors.affiliation: European Molecular Biology Laboratory, Heidelberg, Germany; Molecular Medicine Partnership Unit, University of Heidelberg and European Molecular Biology Laboratory, 69117 Heidelberg, Germany; Max Delbrück Centre for Molecular Medicine, 13125 Berlin, Germany; Department of Bioinformatics, Biocenter, University of Würzburg, 97074 Würzburg, Germany.
authors.forename: Peer
authors.initials: P
authors.lastname: Bork
authors.affiliation: European Molecular Biology Laboratory, Heidelberg, Germany. Electronic address: patil@embl.de.
authors.forename: Kiran Raosaheb
authors.initials: KR
authors.lastname: Patil
mesh_terms: D018407:Bacterial Physiological Phenomena; D001426:Bacterial Proteins / Q000378:metabolism*; D056804:Biofuels / Q000382:microbiology*; D002244:Carbon / Q000378:metabolism*; D049109:Cell Proliferation / Q000502:physiology*; D003198:Computer Simulation; D064688:Metabolic Flux Analysis / Q000379:methods; D053858:Metabolic Networks and Pathways / Q000502:physiology*; D008954:Models, Biological
chemical_list: D001426:Bacterial Proteins; D056804:Biofuels; D002244:Carbon
keywords: Cell factory; Growth-product coupling