title: The missing link in coenzyme A biosynthesis: PanM (formerly YhhK), a yeast GCN5 acetyltransferase homologue triggers aspartate decarboxylase (PanD) maturation in Salmonella enterica.
abstract: Coenzyme A (CoA) is an essential cofactor for all forms of life. The biochemistry underpinning the assembly of CoA in Escherichia coli and other enterobacteria is well understood, except for the events leading to maturation of the L-aspartate-α-decarboxylase (PanD) enzyme that converts pantothenate to β-alanine. PanD is synthesized as pro-PanD, which undergoes an auto-proteolytic cleavage at residue Ser25 to yield the catalytic pyruvoyl moiety of the enzyme. Since 1990, it has been known that E. coli yhhK strains are pantothenate auxotrophs, but the role of YhhK in pantothenate biosynthesis remained an enigma. Here we show that Salmonella enterica yhhK strains are also pantothenate auxotrophs. In vivo and in vitro evidence shows that YhhK interacts directly with PanD, and that such interactions accelerate pro-PanD maturation. We also show that S. enterica yhhK strains accumulate pro-PanD, and that not all pro-PanD proteins require YhhK for maturation. For example, the Corynebacterium glutamicum panD(+) gene corrected the pantothenate auxotrophy of a S. enterica yhhK strain, supporting in vitro evidence obtained by others that some pro-PanD proteins autocleave at faster rates. We propose the name PanM for YhhK to reflect its role as a trigger of pro-PanD maturation by stabilizing pro-PanD in an autocleavage-prone conformation.
authors.affiliation: Department of Bacteriology, University of Wisconsin, Madison, WI 53706-1521, USA.
authors.forename: Tara N
authors.initials: TN
authors.lastname: Stuecker
authors.forename: Kelsey M
authors.initials: KM
authors.lastname: Hodge
authors.forename: Jorge C
authors.initials: JC
authors.lastname: Escalante-Semerena
mesh_terms: D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D002262:Carboxy-Lyases / Q000235:genetics / Q000378:metabolism*; D003065:Coenzyme A / Q000096:biosynthesis*; D048230:Corynebacterium glutamicum; D008969:Molecular Sequence Data; D010205:Pantothenic Acid / Q000378:metabolism; D011485:Protein Binding; D025941:Protein Interaction Mapping; D011499:Protein Processing, Post-Translational; D012486:Salmonella typhimurium / Q000201:enzymology* / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
chemical_list: D010205:Pantothenic Acid; D000123:Acetyltransferases; D002262:Carboxy-Lyases; C019747:aspartate 4-decarboxylase; D003065:Coenzyme A