Biosynthesis of the Multifunctional Isopropylstilbene inPhotorhabdus laumondiiInvolves Cross-Talk between Specialized and Primary Metabolism

Abstract

Isopropylstilbene (IPS) derived from the entomopathogenic bacteriumPhotorhabdusrepresents the only known stilbene which is not produced by a plant stilbene synthase but a bacterial PKS II synthase. While the exclusive cyclization reaction, responsible for the formation of the characteristic iso-branched side-chain of the molecule, was studied in the past, some parts of the biosynthetic route remained elusive. In this study, we revealed the role of StlB that is able to produce CoA-derivatives and demonstrated the elongation of cinnamoyl-CoA with enzymes from the bacterial fatty acid biosynthesis pathway. Thus, we deciphered cross-talk between the enzymes from primary and specialized metabolism. These insights led, for the first time, to the production of IPS in a heterologous host.