Isocoumarin formation by heterologous gene expression and modification by host enzymes

Heterologous expression has been proven to be a successful strategy for the identification of metabolites encoded by cryptic/silent genes. Expression of a nonreducing polyketide synthase (NR-PKS) gene from Penicillium crustosum in Aspergillus nidulans led to the accumulation of three isocoumarins 1-3. Feeding experiments revealed that the PKS product 1 can be converted by the host enzymes to its hydroxylated (2) and methylated (3) derivatives. These results provided one additional example that unexpected further modifications of an enzyme product can take place in a heterologous host.