title: Building the repertoire of dispensable chromosome regions in Bacillus subtilis entails major refinement of cognate large-scale metabolic model.
abstract: The nonessential regions in bacterial chromosomes are ill-defined due to incomplete functional information. Here, we establish a comprehensive repertoire of the genome regions that are dispensable for growth of Bacillus subtilis in a variety of media conditions. In complex medium, we attempted deletion of 157 individual regions ranging in size from 2 to 159 kb. A total of 146 deletions were successful in complex medium, whereas the remaining regions were subdivided to identify new essential genes (4) and coessential gene sets (7). Overall, our repertoire covers ~76% of the genome. We screened for viability of mutant strains in rich defined medium and glucose minimal media. Experimental observations were compared with predictions by the iBsu1103 model, revealing discrepancies that led to numerous model changes, including the large-scale application of model reconciliation techniques. We ultimately produced the iBsu1103V2 model and generated predictions of metabolites that could restore the growth of unviable strains. These predictions were experimentally tested and demonstrated to be correct for 27 strains, validating the refinements made to the model. The iBsu1103V2 model has improved considerably at predicting loss of viability, and many insights gained from the model revisions have been integrated into the Model SEED to improve reconstruction of other microbial models.
authors.affiliation: INRA, UMR 1319 Micalis, AgroParisTech, UMR Micalis, Jouy-en-Josas F-78350, France.
authors.forename: Kosei
authors.initials: K
authors.lastname: Tanaka
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Henry
authors.forename: Jenifer F
authors.initials: JF
authors.lastname: Zinner
authors.forename: Edmond
authors.initials: E
authors.lastname: Jolivet
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Cohoon
authors.forename: Fangfang
authors.initials: F
authors.lastname: Xia
authors.forename: Vladimir
authors.initials: V
authors.lastname: Bidnenko
authors.forename: S Dusko
authors.initials: SD
authors.lastname: Ehrlich
authors.forename: Rick L
authors.initials: RL
authors.lastname: Stevens
authors.forename: Philippe
authors.initials: P
authors.lastname: Noirot
mesh_terms: D001412:Bacillus subtilis / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002876:Chromosomes, Bacterial; D053858:Metabolic Networks and Pathways / Q000235:genetics; D008954:Models, Biological; D010641:Phenotype