RedH and PigC Catalyze the Biosynthesis of Hybrubins via Phosphorylation of 4 '-Methoxy-2,2 '-Bipyrrole-5 '-Carbaldehyde

摘要

Hybrubins are "unnatural" alkaloids with the same 4'-methoxy-2,2'-bipyrrole-5'-methine moiety found in prodiginines and a different ring derived from tetramic acids. Here, we demonstrated that RedH, a homologue of prodigiosin synthetase PigC, was responsible for the biosynthesis of hybrubins A and B in Streptomyces lividans. In vitro reactions indicated that RedH and PigC catalyzed the intermolecular condensation between 4'-methoxy-2,2'-bipyrrole-5'-carbaldehyde (MBC) and (Z)-5-ethylidenetetramic acid (ETA) to produce hybrubin B. Moreover, we demonstrated that RedH and PigC activated MBC via phosphorylation of the aldehyde group to form an intermediate P,-MBC and that the subsequent condensation between P,-MBC and (Z)-5-ethylidenetetramic acid occurs in a nonenzymatic way.