title: Metabolic network rewiring of propionate flux compensates vitamin B12 deficiency in C. elegans.
abstract: Metabolic network rewiring is the rerouting of metabolism through the use of alternate enzymes to adjust pathway flux and accomplish specific anabolic or catabolic objectives. Here, we report the first characterization of two parallel pathways for the breakdown of the short chain fatty acid propionate in Caenorhabditis elegans. Using genetic interaction mapping, gene co-expression analysis, pathway intermediate quantification and carbon tracing, we uncover a vitamin B12-independent propionate breakdown shunt that is transcriptionally activated on vitamin B12 deficient diets, or under genetic conditions mimicking the human diseases propionic- and methylmalonic acidemia, in which the canonical B12-dependent propionate breakdown pathway is blocked. Our study presents the first example of transcriptional vitamin-directed metabolic network rewiring to promote survival under vitamin deficiency. The ability to reroute propionate breakdown according to B12 availability may provide C. elegans with metabolic plasticity and thus a selective advantage on different diets in the wild.
authors.affiliation: Program in Systems Biology, University of Massachusetts Medical School, Worcester, United States.|Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, United States.
authors.forename: Emma
authors.initials: E
authors.lastname: Watson
authors.affiliation: Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Viridiana
authors.initials: V
authors.lastname: Olin-Sandoval
authors.affiliation: Program in Systems Biology, University of Massachusetts Medical School, Worcester, United States.|Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, United States.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Hoy
authors.affiliation: Program in Systems Biology, University of Massachusetts Medical School, Worcester, United States.|Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, United States.
authors.forename: Chi-Hua
authors.initials: CH
authors.lastname: Li
authors.affiliation: Program in Systems Biology, University of Massachusetts Medical School, Worcester, United States.|Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, United States.
authors.forename: Timo
authors.initials: T
authors.lastname: Louisse
authors.affiliation: Department of Computer Science, Princeton University, Princeton, United States.|Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, United States.
authors.forename: Victoria
authors.identifier: 0000-0002-3201-9983
authors.initials: V
authors.lastname: Yao
authors.affiliation: Program in Systems Biology, University of Massachusetts Medical School, Worcester, United States.|Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, United States.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Mori
authors.affiliation: Program in Systems Biology, University of Massachusetts Medical School, Worcester, United States.|Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, United States.
authors.forename: Amy D
authors.initials: AD
authors.lastname: Holdorf
authors.affiliation: Department of Computer Science, Princeton University, Princeton, United States.|Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, United States.|Simons Center for Data Analysis, Simons Foundation, New York, United States.
authors.forename: Olga G
authors.initials: OG
authors.lastname: Troyanskaya
authors.affiliation: Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom.|The Francis Crick Institute, Mill Hill Laboratory, London, United Kingdom.
authors.forename: Markus
authors.identifier: 0000-0001-9535-7413
authors.initials: M
authors.lastname: Ralser
authors.affiliation: Program in Systems Biology, University of Massachusetts Medical School, Worcester, United States.|Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, United States.
authors.forename: Albertha Jm
authors.identifier: 0000-0001-5587-3608
authors.initials: AJ
authors.lastname: Walhout
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism*; D060847:Metabolic Engineering; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D011422:Propionates / Q000378:metabolism*; D014806:Vitamin B 12 Deficiency
chemical_list: D011422:Propionates
keywords: C. elegans; bacteria; chromosomes; computational biology; genes; human; metabolism; network rewiring; propionate; systems biology; transcription; vitamin B12