title: Arrest of cell cycle by inhibition of ribonucleotide reductase induces accumulation of NAD+ by Mn2+-supplemented growth of Corynebacterium ammoniagenes.
abstract: Cell division of the wild type strain Corynebacterium (formerly Brevibacterium) ammoniagenes ATCC 6872 which requires 1 microM Mn2+ for balanced growth was inhibited by addition of 20 mM hydroxyurea (HU) or 10 mM p-methoxyphenol (MP) to a Mn2+-supplemented fermentation medium at an appropriate time. Scanning electron microscopy (SEM) showed a restricted elongation characteristic of arrest of the cell cycle in coryneform bacteria. The cultures treated with HU or MP had, respectively, a fourfold or sixfold enhanced accumulation of NAD+ by a salvage biosynthetic pathway. An assay of nucleotide-permeable cells for ribonucleotide reductase activity using [3H-CDP] as substrate revealed a pre-early and complete decline of DNA precursor biosynthesis not found in the untreated control. Overproduction of NAD+ is an alternative to the conventional fermentation process using Mn2+ deficiency. A simple model is presented to discuss the metabolic regulation of the new process based on the presence of a manganese ribonucleotide reductase (Mn-RNR) in the producing strain.
authors.affiliation: Institut für Mikrobiologie, Universität Hannover, Schneiderberg 50, D-30167 Hannover, Germany.
authors.forename: Bouziane
authors.initials: B
authors.lastname: Abbouni
authors.forename: Hesham M
authors.initials: HM
authors.lastname: Elhariry
authors.forename: Georg
authors.initials: G
authors.lastname: Auling
mesh_terms: D000840:Anisoles / Q000494:pharmacology; D002453:Cell Cycle / Q000502:physiology; D003352:Corynebacterium / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism / Q000648:ultrastructure; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology; D006918:Hydroxyurea / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology*; D009243:NAD / Q000096:biosynthesis*; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000840:Anisoles; D009243:NAD; C009760:mequinol; D012264:Ribonucleotide Reductases; D008274:Magnesium; D006918:Hydroxyurea