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

Abstract

Hybrubins are an emerging class of prodiginines possessing a new C ring derived from 5′-substituted tetramic acids and the methylene bridge connecting the C ring at a different position. We have supposed that condensation between 4′-methoxy-2,2′-bipyrrole-5′-carbaldehyde (MBC) and 5-ethylidenetetramic acid (ETA) yields the hybrid natural products hybrubins, which was proposed to be catalyzed by the undecylprodigiosin synthetase RedH. However, it is doubted whether RedH is able to catalyze another type of condensation between MBC and tetramic acids. In this study, we have demonstrated that the MBC-ETA condensation proceeds through RedH/PigC-catalyzed enzymatic activation of MBC via phosphorylation and a nonenzymatic condensation of P i -MBC with ETA. Since MBC analogues have been shown to be accepted by PigC, more hybrubin analogues might be produced by using combinations of MBC analogues and other tetramic acids in future studies.