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

Abstract

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 has 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.

Iron Homeostasis Regulates the Genotoxicity of Escherichia coli That Produces Colibactin

“…A prerequisite for the synthesis of all NRPs, PKs, and PK-NRP hybrids is the posttranslational attachment of P-Pant arms from coenzyme A (CoA) to a conserved serine residue of a carrier protein, converting inactive apo-synthases to active holo-synthases. This reaction is catalyzed by members of the type II family of phosphopantetheinyl transferases (PPTases) (12). The core genome of Escherichia coli codes for two type II PPTases, i.e., EntD and YieE (ECK3705, b3712, JW3690) (13).…”

A Sfp-type phosphopantetheinyl transferase ZmsO is essential for zeamines production and the virulence of Dickeya zeae

“…It proved that mutation of zmsO will not affect the transcriptional levels of polyketide synthase ZmsA (Zhou et al 2011) and non-ribosomal peptide synthase ZmsK (Cheng et al 2013) in D. zeae. Analysis of the amino acid sequence of ZmsO showed that it is a 4′-phosphopantetheinyl transferase, which usually transform 4′-phosphopantetheine moiety from CoA to apo-CPs to form holo-CPs (Beld et al 2014;Sunbul et al 2009). Previous studies have classified the 4′-phosphopantetheinyl transferases into three types (Beld et al 2014) (Fig.…”

“…Analysis of the amino acid sequence of ZmsO showed that it is a 4′-phosphopantetheinyl transferase, which usually transform 4′-phosphopantetheine moiety from CoA to apo-CPs to form holo-CPs (Beld et al 2014;Sunbul et al 2009). Previous studies have classified the 4′-phosphopantetheinyl transferases into three types (Beld et al 2014) (Fig. 5a).…”

“…This modification is carried out by transformation of 4′-phosphopantetheine moiety from coenzyme A (CoA) to apo-carrier proteins (CPs) to form holo-carrier proteins by phosphopantetheinyl transferase (PPTase) (Beld et al 2014;Sunbul et al 2009). According to the substrate specificity, PPTases were classified into three subtypes.…”

Exploiting the genome sequence of Streptomyces nodosus for enhanced antibiotic production

“…There are three 4′-phosphopantetheine transferases encoded in the S. nodosus genome. These were assigned functions based on size, conserved motifs, and homology to known phosphopantetheinyltransferases (Beld et al, 2014) One, SNOD_19940 protein, is likely to be involved in modifying discrete ACPs involved in fatty acid biosynthesis. Another, SNOD_28340 protein, is likely to be involved in modifying ACP domains in NRPSs and PKSs.…”