Structural Insight into a Novel Formyltransferase and Evolution to a Nonribosomal Peptide Synthetase Tailoring Domain.

Publication Type:

Journal Article


ACS Chem Biol (2018)


<p>Nonribosomal peptide synthetases (NRPSs) increase the chemical diversity of their products by acquiring tailoring domains. Linear gramicidin synthetase starts with a tailoring formylation (F) domain, which likely originated from a sugar formyltransferase (FT) gene. Here, we present studies on an Anoxybacillus kamchatkensis sugar FT representative of the prehorizontal gene transfer FT. Gene cluster analysis reveals that this FT acts on a UDP-sugar in a novel pathway for synthesis of a 7-formamido derivative of CMP-pseudaminic acid. We recapitulate the pathway up to and including the formylation step in vitro, experimentally demonstrating the role of the FT. We also present X-ray crystal structures of the FT alone and with ligands, which unveil contrasts with other structurally characterized sugar FTs and show close structural similarity with the F domain. The structures reveal insights into the adaptations that were needed to co-opt and evolve a sugar FT into a functional and useful NRPS domain.</p>

Atomic coordinates and structure factors for PseJ, PseJ bound to N10-THF, PseJ bound to UDP-4-amino-4,6-dideoxy-l-AltNAc, and PseJ bound to UDP-4,6-dideoxy-4-formamido-l-AltNAc and THF have been deposited in the Protein Data Bank under accession codes 6CI2, 6EDK, 6CI4, and 6CI5, respectively.