Microcin C: Biosynthesis, Mode of Action, and Potential as a Lead in Antibiotics Development

Abstract

The natural compound Microcin C (McC) is a Trojan horse inhibitor of aspartyl tRNA synthetases endowed with strong antibacterial properties, in which a heptapeptide moiety is responsible for active transport of the inhibitory metabolite part into the bacterial cell. The intracellularly formed aspartyl AMP analogue carries a chemically more stable phosphoramidate linkage, in comparison to the labile aspartyl-adenylate, and in addition is esterified with a 3-aminopropyl moiety. Therefore, this compound can target aspartyl-tRNA synthetase. The biochemical production and secretion of McC, and the possibilities to develop new classes of antibiotics using the McC Trojan horse concept in combination with sulfamoylated adenosine analogues will be discussed briefly.

Keywords:

• Microcin C
• aminoacyl tRNA synthetase inhibitors
• antibiotics
• aminoacyl sulfamoyl adenosine

ACKNOWLEDGMENTS

GHMV is a recipient of a Belgian Agency for Innovation by Science and Technology (IWT) Fellowship (SB 81116). We are indebted to Chantal Biernaux for assistance in editing the manuscript.

Supplementary information is available online.