Non-ribosomal peptides produced by minimal and engineered synthetases with terminal reductase domains.

: Non-ribosomal peptide synthetases (NRPSs) utilize terminal reductase domains for 2-electron reduction of the enzyme-bound thioester resulting in the release of the generated peptides as C-terminal aldehydes. Here we reveal the biosynthesis of a pyrazine which originates from an aldehyde-generating minimal NRPS termed ATRed in entomopathogenic Xenorhabdus indica. Furthermore, reductase domains were investigated in terms of NRPS engineering and although no general applicable approach was deduced, we show that they can indeed be used for the production of similar natural and non-natural pyrazinones.