DdaR (PA1196) Regulates Expression of Dimethylarginine Dimethylaminohydrolase for the Metabolism of Methylarginines in Pseudomonas aeruginosa PAO1.
Dimethylarginine dimethylaminohydrolases (DDAHs) catalyze the hydrolysis of methylarginines to yield l-citrulline and methylamines as products. DDAHs and their central roles in methylarginine metabolism have been characterized for eukaryotic cells. While DDAHs are known to exist in some bacteria, includingStreptomyces coelicolorandPseudomonas aeruginosa, the physiological importance and genetic regulation of bacterial DDAHs remain poorly understood. To provide some insight into bacterial methylarginine metabolism, this study focused on identifying the key elements or factors regulating DDAH expression inP. aeruginosaPAO1. First, results revealed thatP. aeruginosacan utilizeNG,NG-dimethyl-l-arginine (ADMA) as a sole source of nitrogen but not carbon. Second, expression of theddaHgene was observed to be induced in the presence of methylarginines, includingNG-monomethyl-l-arginine (l-NMMA) and ADMA. Third, induction of theddaHgene was shown to be achieved through a mechanism consisting of the putative enhancer-binding protein PA1196 and the alternative sigma factor RpoN. Both PA1196 and RpoN were essential for the expression of theddaHgene in response to methylarginines. On the basis of the results of this study, PA1196 was given the name DdaR, fordimethylargininedimethylaminohydrolaseregulator. Interestingly, DdaR and its targetddaHgene are conserved only amongP. aeruginosastrains, suggesting that this particularPseudomonasspecies has evolved to utilize methylarginines from its environment.IMPORTANCEMethylated arginine residues are common constituents of eukaryotic proteins. During proteolysis, methylarginines are released in their free forms and become accessible nutrients for bacteria to utilize as growth substrates. In order to have a clearer and better understanding of this process, we explored methylarginine utilization in the metabolically versatile bacteriumPseudomonas aeruginosaPAO1. Our results show that the transcriptional regulator DdaR (PA1196) and the sigma factor RpoN positively regulate expression of dimethylarginine dimethylaminohydrolases (DDAHs) in response to exogenous methylarginines. DDAH is the central enzyme of methylarginine degradation, and its transcriptional regulation by DdaR-RpoN is expected to be conserved amongP. aeruginosastrains.
Department of Chemistry, State University of New York, College of Environmental Science and Forestry, Syracuse, New York, USA.
Benjamin R
BR
Lundgren
Department of Chemistry, State University of New York, College of Environmental Science and Forestry, Syracuse, New York, USA.
Frank J
FJ
Bailey
Department of Chemistry, State University of New York, College of Environmental Science and Forestry, Syracuse, New York, USA.
Gabriella
G
Moley
Department of Chemistry, State University of New York, College of Environmental Science and Forestry, Syracuse, New York, USA ctnomura@esf.edu.|Center for Applied Microbiology, State University of New York, College of Environmental Science and Forestry, Syracuse, New York, USA.|Hubei Collaborative Innovation Center for Green Transformation of Bio-Resources, College of Life Sciences, Hubei University, Wuhan, People's Republic of China.
Christopher T
http://orcid.org/0000-0001-6981-5679
CT
Nomura
D000581:Amidohydrolases / Q000235:genetics / Q000378:metabolism*; D001120:Arginine / Q000031:analogs & derivatives* / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D011550:Pseudomonas aeruginosa / Q000201:enzymology* / Q000378:metabolism; D051877:RNA Polymerase Sigma 54 / Q000235:genetics / Q000378:metabolism; D019323:omega-N-Methylarginine / Q000235:genetics / Q000378:metabolism*
D001426:Bacterial Proteins; D019323:omega-N-Methylarginine; C024917:symmetric dimethylarginine; C018524:N,N-dimethylarginine; D001120:Arginine; D051877:RNA Polymerase Sigma 54; D000581:Amidohydrolases; C059999:dimethylargininase
ADMA; DdaR; PA1196; Pseudomonas aeruginosa; RpoN; dimethylarginine dimethylaminohydrolase; enhancer-binding protein; methylarginine