The phosphopantetheinyl transferases: catalysis of a post-translational modification crucial for life

Covering: up to 2013 Although holo -acyl carrier protein synthase, AcpS, a phosphopantetheinyl transferase (PPTase), was characterized in the 1960s, it was not until the publication of the landmark paper by Lambalot et al. in 1996 that PPTases garnered wide-spread attention being classified as a distinct enzyme superfamily. In the past two decades an increasing number of papers have been published on PPTases ranging from identification, characterization, structure determination, mutagenesis, inhibition, and engineering in synthetic biology. In this review, we comprehensively discuss all current knowledge on this class of enzymes that post-translationally install a 4′-phosphopantetheine arm on various carrier proteins. The phosphopantetheinyl transferase transfers a 4′-phosphopantetheine to a conserved serine on the carrier protein. This post-translational modification is essential for activation of primary and secondary metabolism. Further, the unique enzymatic activity allows for biotechnological applications and drug targeting.