Functional identification of bacterial spermine, thermospermine, norspermine, norspermidine, spermidine, and N1-aminopropylagmatine synthases

Bin Li; Jue Liang; Hamid R Baniasadi; Shin Kurihara; Margaret A Phillips; Anthony J Michael

doi:10.1016/j.jbc.2024.107281

Functional identification of bacterial spermine, thermospermine, norspermine, norspermidine, spermidine, and N¹-aminopropylagmatine synthases

J Biol Chem. 2024 Apr 6;300(5):107281. doi: 10.1016/j.jbc.2024.107281. Online ahead of print.

Authors

Bin Li¹, Jue Liang¹, Hamid R Baniasadi¹, Shin Kurihara², Margaret A Phillips¹, Anthony J Michael³

Affiliations

¹ Department of Biochemistry, UT Southwestern Medical Center, Dallas, Texas, USA.
² Faculty of Biology-Oriented Science and Technology, Kindai University, Kinokawa, Wakayama, Japan.
³ Department of Biochemistry, UT Southwestern Medical Center, Dallas, Texas, USA. Electronic address: anthony.michael@utsouthwestern.edu.

Abstract

Spermine synthase is an aminopropyltransferase that adds an aminopropyl group to the essential polyamine spermidine to form tetraamine spermine, needed for normal human neural development, plant salt and drought resistance, and yeast CoA biosynthesis. We functionally identify for the first time bacterial spermine synthases, derived from phyla Bacillota, Rhodothermota, Thermodesulfobacteriota, Nitrospirota, Deinococcota, and Pseudomonadota. We also identify bacterial aminopropyltransferases that synthesize the spermine same mass isomer thermospermine, from phyla Cyanobacteriota, Thermodesulfobacteriota, Nitrospirota, Dictyoglomota, Armatimonadota, and Pseudomonadota, including the human opportunistic pathogen Pseudomonas aeruginosa. Most of these bacterial synthases were capable of synthesizing spermine or thermospermine from the diamine putrescine and so possess also spermidine synthase activity. We found that most thermospermine synthases could synthesize tetraamine norspermine from triamine norspermidine, that is, they are potential norspermine synthases. This finding could explain the enigmatic source of norspermine in bacteria. Some of the thermospermine synthases could synthesize norspermidine from diamine 1,3-diaminopropane, demonstrating that they are potential norspermidine synthases. Of 18 bacterial spermidine synthases identified, 17 were able to aminopropylate agmatine to form N¹-aminopropylagmatine, including the spermidine synthase of Bacillus subtilis, a species known to be devoid of putrescine. This suggests that the N¹-aminopropylagmatine pathway for spermidine biosynthesis, which bypasses putrescine, may be far more widespread than realized and may be the default pathway for spermidine biosynthesis in species encoding L-arginine decarboxylase for agmatine production. Some thermospermine synthases were able to aminopropylate N¹-aminopropylagmatine to form N¹²-guanidinothermospermine. Our study reveals an unsuspected diversification of bacterial polyamine biosynthesis and suggests a more prominent role for agmatine.

Keywords: N(1)-aminopropylagmatine; bacterial metabolism; biosynthesis; norspermidine; norspermine; polyamine; spermidine; spermine; thermospermine.