title: Investigations into the Biosynthesis, Regulation, and Self-Resistance of Toxoflavin in Pseudomonas protegens Pf-5.
abstract: Pseudomonas spp. are prolific producers of natural products from many structural classes. Here we show that the soil bacterium Pseudomonas protegens Pf-5 is capable of producing trace levels of the triazine natural product toxoflavin (1) under microaerobic conditions. We evaluated toxoflavin production by derivatives of Pf-5 with deletions in specific biosynthesis genes, which led us to propose a revised biosynthetic pathway for toxoflavin that shares the first two steps with riboflavin biosynthesis. We also report that toxM, which is not present in the well-characterized cluster of Burkholderia glumae, encodes a monooxygenase that degrades toxoflavin. The toxoflavin degradation product of ToxM is identical to that of TflA, the toxoflavin lyase from Paenibacillus polymyxa. Toxoflavin production by P. protegens causes inhibition of several plant-pathogenic bacteria, and introduction of toxM into the toxoflavin-sensitive strain Pseudomonas syringae DC3000 results in resistance to toxoflavin.
authors.affiliation: College of Pharmacy, Oregon State University, 203 Pharmacy Building, Corvallis, OR 97331 (USA). benjamin.philmus@oregonstate.edu.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Philmus
authors.affiliation: Agricultural Research Service, US Department of Agriculture, 3420 N.W. Orchard Avenue, Corvallis, OR 97330 (USA).
authors.forename: Brenda T
authors.initials: BT
authors.lastname: Shaffer
authors.affiliation: Agricultural Research Service, US Department of Agriculture, 3420 N.W. Orchard Avenue, Corvallis, OR 97330 (USA).
authors.forename: Teresa A
authors.initials: TA
authors.lastname: Kidarsa
authors.affiliation: Department of Botany and Plant Pathology, Oregon State University, 2082 Cordley Hall, Corvallis, OR 97331 (USA).
authors.forename: Qing
authors.initials: Q
authors.lastname: Yan
authors.affiliation: Department of Microbial Ecology, Netherlands Institute of Ecology, Droevendaalsesteeg 10, 6708 PB Wageningen (The Netherlands).|Institute of Biology, Leiden University, Sylviusweg 72, 2333 BE Leiden (The Netherlands).
authors.forename: Jos M
authors.initials: JM
authors.lastname: Raaijmakers
authors.affiliation: Department of Chemistry, Texas A&M University, College Station, TX 77843 (USA).
authors.forename: Tadhg P
authors.initials: TP
authors.lastname: Begley
authors.affiliation: Agricultural Research Service, US Department of Agriculture, 3420 N.W. Orchard Avenue, Corvallis, OR 97330 (USA). joyce.loper@ars.usda.gov.|Department of Botany and Plant Pathology, Oregon State University, 2082 Cordley Hall, Corvallis, OR 97331 (USA). joyce.loper@ars.usda.gov.
authors.forename: Joyce E
authors.initials: JE
authors.lastname: Loper
mesh_terms: D053898:Biosynthetic Pathways; D002853:Chromatography, Liquid; D003001:Cloning, Molecular; D015394:Molecular Structure; D005810:Multigene Family / Q000235:genetics; D011549:Pseudomonas / Q000235:genetics* / Q000378:metabolism*; D011744:Pyrimidinones / Q000378:metabolism*; D014227:Triazines / Q000378:metabolism*
chemical_list: D011744:Pyrimidinones; D014227:Triazines; C009570:toxoflavin
keywords: biocontrol; natural products; secondary metabolism; triazine