Quinolone-containing
natural products are widely found in bacteria,
fungi, and plants. The fungal quinolactacins, which are N-methyl-4-quinolones, display a wide spectrum of biological activities.
Here we uncovered a concise nonribosomal peptide synthetase pathway
involved in quinolactacin A biosynthesis from Penicillium by using heterologous reconstitution and in vitro enzymatic synthesis. The N-desmethyl analog of
quinolactacin A was accessed through the construction of a hybrid
bacterial and fungi pathway in the heterologous host.