title: The circadian oscillator in Synechococcus elongatus controls metabolite partitioning during diurnal growth.
abstract: Synechococcus elongatus PCC 7942 is a genetically tractable model cyanobacterium that has been engineered to produce industrially relevant biomolecules and is the best-studied model for a prokaryotic circadian clock. However, the organism is commonly grown in continuous light in the laboratory, and data on metabolic processes under diurnal conditions are lacking. Moreover, the influence of the circadian clock on diurnal metabolism has been investigated only briefly. Here, we demonstrate that the circadian oscillator influences rhythms of metabolism during diurnal growth, even though light-dark cycles can drive metabolic rhythms independently. Moreover, the phenotype associated with loss of the core oscillator protein, KaiC, is distinct from that caused by absence of the circadian output transcriptional regulator, RpaA (regulator of phycobilisome-associated A). Although RpaA activity is important for carbon degradation at night, KaiC is dispensable for those processes. Untargeted metabolomics analysis and glycogen kinetics suggest that functional KaiC is important for metabolite partitioning in the morning. Additionally, output from the oscillator functions to inhibit RpaA activity in the morning, and kaiC-null strains expressing a mutant KaiC phosphomimetic, KaiC-pST, in which the oscillator is locked in the most active output state, phenocopies a ΔrpaA strain. Inhibition of RpaA by the oscillator in the morning suppresses metabolic processes that normally are active at night, and kaiC-null strains show indications of oxidative pentose phosphate pathway activation as well as increased abundance of primary metabolites. Inhibitory clock output may serve to allow secondary metabolite biosynthesis in the morning, and some metabolites resulting from these processes may feed back to reinforce clock timing.
authors.affiliation: Center for Circadian Biology, California Center for Algal Biotechnology, Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093.
authors.forename: Spencer
authors.initials: S
authors.lastname: Diamond
authors.affiliation: Center for Circadian Biology, California Center for Algal Biotechnology, Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093.
authors.forename: Darae
authors.initials: D
authors.lastname: Jun
authors.affiliation: Center for Circadian Biology, California Center for Algal Biotechnology, Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093.
authors.forename: Benjamin E
authors.initials: BE
authors.lastname: Rubin
authors.affiliation: Center for Circadian Biology, California Center for Algal Biotechnology, Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093 sgolden@ucsd.edu.
authors.forename: Susan S
authors.initials: SS
authors.lastname: Golden
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001683:Biological Clocks; D050260:Carbohydrate Metabolism / Q000235:genetics / Q000528:radiation effects; D002940:Circadian Rhythm; D056925:Circadian Rhythm Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D003624:Darkness; D006003:Glycogen / Q000378:metabolism; D007700:Kinetics; D008027:Light; D050356:Lipid Metabolism / Q000235:genetics / Q000528:radiation effects; D053858:Metabolic Networks and Pathways / Q000235:genetics / Q000528:radiation effects; D055442:Metabolome / Q000235:genetics / Q000528:radiation effects; D055432:Metabolomics / Q000379:methods; D008954:Models, Biological; D009154:Mutation; D009711:Nucleotides / Q000378:metabolism; D046940:Synechococcus / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors
chemical_list: D000596:Amino Acids; D001426:Bacterial Proteins; D056925:Circadian Rhythm Signaling Peptides and Proteins; C114271:KaiC protein, cyanobacteria; D009711:Nucleotides; D006003:Glycogen
keywords: circadian clock; cyanobacteria; diurnal; metabolism; metabolomics
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