The ancient roots of nicotianamine: diversity, role, regulation and evolution of nicotianamine-like metallophores

Clémentine Laffont (1) , Pascal Arnoux (1)

1 BIAM - Institut de Biosciences et Biotechnologies d'Aix-Marseille (ex-IBEB)

Nicotianamine(NA)isametabolitesynthesized by allplantsinwhichitisinvolved inthe homeostasisofdifferentmicronutrientssuchasiron,nickelorzinc.Insomeplantsitalso serves as a precursor of phytosiderophores that are used for extracellular iron scavenging.PreviousworkshavealsoestablishedthepresenceofNA infilamentousfungi andsomemosseswhereasananalogueofNAwasinferredinanarchaea.Morerecently, opine-typemetallophoreswithhomologytoNAwereuncoveredinbacteria, especiallyin human pathogens such as Staphylococcus aureus, Pseudomonas aeruginosa or Yersinia pestis, synthesizing respectively staphylopine, pseudopalineand yersinopine.Here, we reviewthecurrentstateofknowledgeregardingthediscovery,biosynthesis,functionand regulationofthesemetallophores.WealsodiscussthegenomicenvironmentofthecntL gene,whichishomologous totheplantNAsynthase(NAS)gene,andplaysacentralrole inthesynthesisofNA-like metallophores.Thisreveals alargediversityofbiosynthetic, export and import pathways.Using sequence similarity networks, we uncovered that these metallophores are widespread in numerous bacteria thriving in very different environments,suchasthose livingatthehost-pathogeninterfacebutalsointhe soil. We additionally establishedaphylogenyoftheNAS/cntLgeneand,asaresult,wepropose thatthisgene isanancientgeneandNA, oritsderivatives, isan ancientmetallophore that playedaprominentroleinmetalacquisition ormetalresistance.Indeed,ourphylogenetic analysis suggests an evolutionary model where the possibility to synthesize this metallophore waspresentearlyintheapparitionoflife, althoughit waslaterlostbymost living microorganisms, unless facing metal starvation such as at the host-pathogen interface or in some soils. According to our model, NA then re-emerged as a central metabolitefor metalhomeostasis in fungi,mossesandallknownhigherplants.

Domaines: Sciences du Vivant [q-bio]; Chimie

Clémentine Laffont, Pascal Arnoux. The ancient roots of nicotianamine: diversity, role, regulation and evolution of nicotianamine-like metallophores. Metallomics, 2020, 12 (10), pp.1480-1493. ⟨10.1039/D0MT00150C⟩. ⟨cea-03125731⟩