Biosynthesis of a 'fungal' peptide antibiotic by Burkholderia gladioli

Burkholderia are a multitalented genus of Gram-negative bacteria that we have recently shown to be a promising, untapped source of antibiotics with the potential to overcome antimicrobial resistance [1]. In particular, Burkholderia gladioli, a species which is a common cause of lung infection in cystic fibrosis (CF) patients was found to excrete both antifungal and antibacterial metabolites[2]. In the process of screening B. gladioli isolates, a cyclic peptolide antibiotic active against S. pyogenes, S. pneumonia and E. faecalis, originally reported as a metabolite of a fungus, was discovered. Genome sequencing of several B. gladioli isolates using Pacific Biosciences SMRT technology identified a single, putative biosynthetic gene encoding a non-ribosomal peptide synthetase (NRPS) congruent with the biosynthesis of the antibiotic. The modular NRPS exhibits an unprecedented architecture which implicating cross-talk between fatty acid and non-ribosomal peptide biosynthesis. Inactivation of the gene abolished production of the antibiotic, confirming that the NRPS is involved in the biosynthesis. Our data suggest that an endosymbiotic bacterium harboured by the fungus is the true producer of the antibiotic, providing a second example of bioactive natural product biosynthesis via such a symbioisis [3].