UDP-N-acetylglucosamine--undecaprenyl-phosphate N-acetylglucosaminylphosphotransferase (TarO) (TarO)

TarO, formally known as UDP-N-acetylglucosamine--undecaprenyl-phosphate N-acetylglucosaminylphosphotransferase, is the initiating enzyme in the wall teichoic acid (WTA) biosynthetic pathway of Gram-positive bacteria, most notably Staphylococcus aureus. It catalyzes the transfer of N-acetylglucosamine-1-phosphate from UDP-GlcNAc to an undecaprenyl-phosphate carrier in the cytoplasmic membrane. While the TarO enzyme is not essential for bacterial survival under standard laboratory conditions, its activity is critical for the proper assembly of the cell wall and the display of surface proteins. Inhibition of TarO results in a complete loss of WTAs, which significantly attenuates bacterial virulence and restores the susceptibility of methicillin-resistant S. aureus (MRSA) to beta-lactam antibiotics. This 'synthetic lethal' relationship makes TarO a high-priority target for the development of resistance-modifying agents that can restore the efficacy of existing antibiotics. Several small molecules, including the tarocins and tunicamycin, have been identified as TarO inhibitors, though therapeutic development requires careful management of selectivity to avoid cross-reactivity with similar human transferases.

Other names

TagOLlmGlcNAc-P-transferaseUDP-GlcNAc:undecaprenyl-phosphate GlcNAc-1-phosphate transferase

Inhibition of the first committed step of wall teichoic acid (WTA) biosynthesis