title: Biotechnological production and application of the antibiotic pimaricin: biosynthesis and its regulation.
abstract: Pimaricin (natamycin) is a small polyene macrolide antibiotic used worldwide. This efficient antimycotic and antiprotozoal agent, produced by several soil bacterial species of the genus Streptomyces, has found application in human therapy, in the food and beverage industries and as pesticide. It displays a broad spectrum of activity, targeting ergosterol but bearing a particular mode of action different to other polyene macrolides. The biosynthesis of this only antifungal agent with a GRAS status has been thoroughly studied, which has permitted the manipulation of producers to engineer the biosynthetic gene clusters in order to generate several analogues. Regulation of its production has been largely unveiled, constituting a model for other polyenes and setting the leads for optimizing the production of these valuable compounds. This review describes and discusses the molecular genetics, uses, mode of action, analogue generation, regulation and strategies for increasing pimaricin production yields.
authors.affiliation: Area of Microbiology, Faculty of Biology, Universidad de León, 24071, León, Spain. jesus.aparicio@unileon.es.
authors.forename: Jesús F
authors.identifier: http://orcid.org/0000-0003-4242-4701
authors.initials: JF
authors.lastname: Aparicio
authors.affiliation: Area of Microbiology, Faculty of Biology, Universidad de León, 24071, León, Spain.
authors.forename: Eva G
authors.initials: EG
authors.lastname: Barreales
authors.affiliation: Area of Microbiology, Faculty of Biology, Universidad de León, 24071, León, Spain.
authors.forename: Tamara D
authors.initials: TD
authors.lastname: Payero
authors.affiliation: Dynamique des Génomes et Adaptation Microbienne, UMR 1128, INRA, Université de Lorraine, 54506, Vandoeuvre-lès-Nancy, France.
authors.forename: Cláudia M
authors.initials: CM
authors.lastname: Vicente
authors.affiliation: Area of Microbiology, Faculty of Biology, Universidad de León, 24071, León, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: de Pedro
authors.affiliation: Department of Molecular Microbiology, John Innes Centre, Norwich Research Park, Norwich, NR4 7UH, UK.
authors.forename: Javier
authors.initials: J
authors.lastname: Santos-Aberturas
mesh_terms: D000935:Antifungal Agents / Q000378:metabolism*; D053898:Biosynthetic Pathways / Q000235:genetics*; D001709:Biotechnology / Q000379:methods*; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D010866:Natamycin / Q000096:biosynthesis*; D013302:Streptomyces / Q000235:genetics* / Q000378:metabolism*
chemical_list: D000935:Antifungal Agents; D010866:Natamycin
keywords: Antifungal agent; Cheese; Gene regulation; Keratitis; Metabolic engineering; Polyene macrolide; Preservative E-235; Streptomyces