title: The Essential Role of Spermidine in Growth of Agrobacterium tumefaciens Is Determined by the 1,3-Diaminopropane Moiety.
abstract: The ubiquitous polyamine spermidine is indispensable for eukaryotic growth and cell proliferation. A conserved vital function of spermidine across eukaryotes is conferred by its aminobutyl group that is transferred to a single lysine in translation factor eIF5A to form the essential hypusine post-translational modification required for cellular translation. In direct contrast, although spermidine is absolutely essential for growth of α-proteobacterial plant pathogen Agrobacterium tumefaciens, we have found, by employing a suite of natural polyamines and synthetic methylated spermidine analogues together with spermidine biosynthetic mutants, that it is solely the 1,3-diaminopropane moiety of spermidine that is required for growth. Indeed, any polyamine containing an intact terminal 1,3-diaminopropane moiety can replace spermidine for growth, including the simple diamine 1,3-diaminopropane itself, a paradigm shift in understanding polyamine function in bacteria. We have identified for the first time a spermidine retroconversion activity in bacteria, producing diamine putrescine from triamine spermidine; however, exogenously supplied tetraamine spermine is resistant to retroconversion. When spermidine levels are pharmacologically decreased, synthesis of spermine from spermidine is induced via the same biosynthetic enzymes, carboxyspermidine dehydrogenase and carboxyspermidine decarboxylase that produce spermidine from putrescine, the first identification of a spermine biosynthetic pathway in bacteria. This also suggests that spermidine represses spermine biosynthesis, but when spermidine levels decrease, it is then converted by carboxyspermidine dehydrogenase and decarboxylase enzymes to spermine, which is resistant to retroconversion and constitutes a sequestered pool of protected 1,3-diaminopropane modules required for growth. We also identify an efficient N-acetylspermidine deacetylase activity, indicative of a sophisticated bacterial polyamine homeostasis system.
authors.affiliation: Department of Pharmacology, University of Texas Southwestern Medical Center , Dallas, Texas 75390, United States.
authors.forename: Sok Ho
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Biology, Indiana University , Bloomington, Indiana 47405, United States.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences , Vavilov Street 32, Moscow 119991, Russia.
authors.forename: Maxim
authors.initials: M
authors.lastname: Khomutov
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences , Vavilov Street 32, Moscow 119991, Russia.
authors.forename: Alexey
authors.initials: A
authors.lastname: Khomutov
authors.affiliation: Department of Biology, Indiana University , Bloomington, Indiana 47405, United States.
authors.forename: Clay
authors.initials: C
authors.lastname: Fuqua
authors.affiliation: Department of Pharmacology, University of Texas Southwestern Medical Center , Dallas, Texas 75390, United States.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Michael
mesh_terms: D000107:Acetylation; D016960:Agrobacterium tumefaciens / Q000737:chemistry / Q000254:growth & development* / Q000378:metabolism; D003959:Diamines / Q000737:chemistry / Q000378:metabolism; D011407:Propane / Q000031:analogs & derivatives / Q000378:metabolism; D013095:Spermidine / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism*
chemical_list: D003959:Diamines; C017988:N(1)-acetylspermidine; D011407:Propane; D013095:Spermidine