Peucemycin

[1] This compound was elucidated from a cryptic biosynthetic gene cluster and is produced under temperature-specific conditions for bacterial growth (metabolite is present at 18 °C but not 28 °C).

[2] Peucemycin has demonstrated bioactivity against growth of S. aureus, P. hauseri, and S. enterica and also is weakly active against cancer cell lines.

[2] Peucemycin is synthesized through a type 1 polyketide synthase with 8 proposed modules from 5 PKS-related genes (peuA-peuE).

Sequencing data of Module 4 indicates presence of a dehydratase enzyme, but amino acid mutations leave this enzyme inactivated, meaning a singular hydroxyl group at carbon 9 is generated.

The forming polyketide chain is hydroxylated with cytochrome P450 enzymes, peuH and peuG, and the terminal thioesterase domain in Module 7 catalyzes the product release and macrocycle formation to form peucemycin.

Figure 1. Biosynthesis of Peucemycin via Type 1 PKS system. Enzymes are shown in colored circles and butyl malonyl-CoA moeity introduced by peuI is highlighted in yellow.