A conserved transcription factor controls gluconeogenesis via distinct targets in hypersaline-adapted archaea with diverse metabolic capabilities

Abstract

AbstractTimely regulation of carbon metabolic pathways is essential for cellular processes and to prevent futile cycling of intracellular metabolites. InHalobacterium salinarum, a hypersaline adapted archaeon, a sugar-sensing TrmB family protein controls gluconeogenesis and other biosynthetic pathways. Notably,Hbt. salinarumdoes not utilize carbohydrates for energy, uncommon among Haloarchaea. We characterized a TrmB-family transcriptional regulator in a saccharolytic generalist,Haloarcula hispanica, to investigate whether the targets and function of TrmB, or its regulon, is conserved in related species with distinct metabolic capabilities. InHar. hispanica, TrmB binds to 15 sites across the genome and induces the expression of genes primarily involved in gluconeogenesis and tryptophan biosynthesis. An important regulatory control point inHbt. salinarum, activation ofppsAand repression ofpykA, is absent inHar. hispanica. Contrary to its role inHbt. salinarumand saccharolytic hyperthermophiles, TrmB does not act as a global regulator: it does not directly repress the expression of glycolytic enzymes, peripheral pathways such as cofactor biosynthesis, or catabolism of other carbon sources inHar. hispanica. Cumulatively, these findings suggest re-wiring of the TrmB regulon alongside metabolic network evolution in Haloarchaea.