title: Biosynthesis of antifungal and antibacterial polyketides by Burkholderia gladioli in coculture with Rhizopus microsporus.
abstract: Fungi-bacteria interactions can impact the course of fungal infection and biotechnological use. The mucoralean fungus Rhizopus microsporus, traditionally used in food fermentations (tempe and sufu), is frequently accompanied by Burkholderia gladioli pv. cocovenenans. When producing tempe bongkrek, the bacterial contamination can lead to lethal food-related intoxications caused by the respiratory toxin bongkrekic acid. To unveil the metabolic potential of the fungus-associated bacterium, we sequenced its genome, assigned secondary metabolite biosynthesis gene clusters and monitored the metabolic profile under various growth conditions. In addition to the bongkrekic acid biosynthesis gene cluster we found gene clusters coding for the biosynthesis of toxoflavin and a complex polyketide. The orphan polyketide synthase gene cluster was activated under conditions that emulate tempe production, which enabled isolation and structure elucidation of four members of the enacyloxin family of antibiotics, out of which one is new. Moreover, we found that the fungus positively influences the growth of the bacteria and dramatically increases bongkrekic acid production in stationary culture, which inhibits the growth of the fungus. These results showcase the context-dependent formation of antifungal and antibacterial agents at the fungal-bacterial interface, which may also serve as a model for scenarios observed in mixed infections.
authors.affiliation: Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute (HKI), Jena, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Ross
authors.forename: Viktoria
authors.initials: V
authors.lastname: Opel
authors.forename: Kirstin
authors.initials: K
authors.lastname: Scherlach
authors.forename: Christian
authors.initials: C
authors.lastname: Hertweck
mesh_terms: D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000494:pharmacology; D000935:Antifungal Agents / Q000378:metabolism* / Q000494:pharmacology; D001865:Bongkrekic Acid / Q000096:biosynthesis; D042725:Burkholderia gladioli / Q000235:genetics / Q000378:metabolism*; D018920:Coculture Techniques; D019295:Computational Biology; D005810:Multigene Family; D061065:Polyketides / Q000378:metabolism / Q000494:pharmacology*; D012233:Rhizopus / Q000235:genetics / Q000378:metabolism*; D017422:Sequence Analysis, DNA
chemical_list: D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D061065:Polyketides; D001865:Bongkrekic Acid
keywords: Mucorales; bongkrekic acid; enacyloxin; genome mining; natural products; toxoflavin