Molecular Mechanism for the Biosynthesis and Regulation of Secondary Metabolites in Lysobacter

Lysobacter enzymogenes, a Gram-negative microorganism, is a source of potentially novel bioactive secondary metabolites such as HSAF, WAP-8294A, and aryl polyene pigments. Extensive research has been carried out to study the mechanism of biosynthesis of these metabolites. However, the molecular regulations of these natural products are not well understood so far. In the present study, we provided the first report that 3-hydroxybenzoic acid (3-HBA) and 4-hydroxybenzoic acid (4-HBA) serve as diffusible factors capable of regulating HSAF biosynthesis in L. enzymogenes. We found L. enzymogenes utilized LenB2 as a bifunctional chorismatase to convert chorismate to 4-HBA and 3-HBA. Mutation of lenB2 almost completely abolished the production of 4-HBA and 3-HBA, leading to a complete stop of HSAF production, whereas overexpression of lenB2 increased the production of HSAF. The results show that 3-HBA and 4-HBA are diffusible signaling molecules modulating the HSAF biosynthesis in L. enzymogenes. This finding expands our understanding of the biological roles played by the widely distributed benzoic acid derivatives in bacteria.