D-alanyl carrier protein ligase (DltA)

D-alanyl carrier protein ligase (DltA) is an ATP-dependent enzyme that catalyzes the first committed step in the D-alanylation pathway of teichoic acids in Gram-positive bacteria, such as Staphylococcus aureus and Bacillus species[4][2][5]. It activates D-alanine by adenylation and subsequently ligates it to the 4′-phosphopantetheinyl group of the carrier protein DltC, providing the essential intermediate for the modification of wall and membrane teichoic acids with D-alanine residues[2][3]. This modification alters the anionic charge of the bacterial cell wall, impacting cell wall stability, autolysis, biofilm formation, and resistance to host antimicrobial peptides and antibiotics[4]. Deprivation of D-alanine from teichoic acids due to DltA inactivation increases the sensitivity of pathogens like methicillin-resistant S. aureus to antibiotics and host defenses, making DltA an attractive target for novel antibacterial therapy[4][5]. The enzyme displays unique substrate and enantiomer specificity, favoring D-alanine over L-alanine due to conserved structural determinants[2][5]. The DltABCD operon encodes the complete pathway for D-alanylation, with DltA being the first and essential enzyme in this sequence[4][2].

Other names

D-alanine-Dcp ligaseD-alanyl carrier protein synthaseD-alanyl-ACP ligase

Enzymatic ligation of D-alanine to a carrier protein (DltC), enabling subsequent transfer to teichoic acids in the bacterial cell wall[2][4][5].