title: Integration of Biomass Formulations of Genome-Scale Metabolic Models with Experimental Data Reveals Universally Essential Cofactors in Prokaryotes.
abstract: The composition of a cell in terms of macromolecular building blocks and other organic molecules underlies the metabolic needs and capabilities of a species. Although some core biomass components such as nucleic acids and proteins are evident for most species, the essentiality of the pool of other organic molecules, especially cofactors and prosthetic groups, is yet unclear. Here we integrate biomass compositions from 71 manually curated genome-scale models, 33 large-scale gene essentiality datasets, enzyme-cofactor association data and a vast array of publications, revealing universally essential cofactors for prokaryotic metabolism and also others that are specific for phylogenetic branches or metabolic modes. Our results revise predictions of essential genes in Klebsiella pneumoniae and identify missing biosynthetic pathways in models of Mycobacterium tuberculosis. This work provides fundamental insights into the essentiality of organic cofactors and has implications for minimal cell studies as well as for modeling genotype-phenotype relations in prokaryotic metabolic networks.
authors.affiliation: CEB - Centre of Biological Engineering, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal; Structural and Computational Biology Unit, European Molecular Biology Laboratory, Meyerhofstraße 1, 69117 Heidelberg, Germany. Electronic address: joanarcxavier@ceb.uminho.pt.
authors.forename: Joana C
authors.initials: JC
authors.lastname: Xavier
authors.affiliation: Structural and Computational Biology Unit, European Molecular Biology Laboratory, Meyerhofstraße 1, 69117 Heidelberg, Germany. Electronic address: patil@embl.de.
authors.forename: Kiran Raosaheb
authors.initials: KR
authors.lastname: Patil
authors.affiliation: CEB - Centre of Biological Engineering, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal. Electronic address: irocha@deb.uminho.pt.
authors.forename: Isabel
authors.initials: I
authors.lastname: Rocha
mesh_terms: D001419:Bacteria / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D018533:Biomass; D002874:Chromosome Mapping / Q000379:methods*; D003067:Coenzymes / Q000235:genetics / Q000378:metabolism*; D003198:Computer Simulation; D064688:Metabolic Flux Analysis / Q000379:methods; D053858:Metabolic Networks and Pathways / Q000502:physiology*; D055442:Metabolome / Q000502:physiology*; D008954:Models, Biological; D018511:Systems Integration
chemical_list: D001426:Bacterial Proteins; D003067:Coenzymes
keywords: Coenzyme A (PubChem CID: 87642); Essential cofactors; Flavin Adenine Dinucleotide (PubChem CID: 643975); Flavin mononucleotide (PubChem CID: 643976); Genome-scale models; Metabolic networks; NAD+(PubChem CID: 5892); NADP+(PubChem CID: 5886); Pyridoxal 5′-phosphate (PubChem CID: 1051); S-adenosylmethionine (PubChem CID: 34755); Tetrahydrofolate (PubChem CID: 91443); Tetrahydromethanopterin (PubChem CID: 5462234); Thiamine diphosphate (PubChem CID: 1132)