title: Crosstalk of Nataxazole Pathway with Chorismate-Derived Ionophore Biosynthesis Pathways in Streptomyces sp. Tü 6176.
abstract: Streptomyces sp. Tü 6176, producer of cytotoxic benzoxazoles AJI9561, nataxazole, and 5-hydroxy-nataxazole, has been found to produce a fourth benzoxazole, UK-1. All derive from 3-hydroxy-anthranilate synthesized by the nataxazole biosynthesis machinery. However, biosynthesis of AJI9561, nataxazole, and 5-hydroxy-nataxazole requires 6-methylsalicylic acid also provided by nataxazole biosynthesis pathway, while biosynthesis of UK-1 utilizes salicylic acid produced by a salicylate synthase from the coelibactin biosynthesis pathway. This clearly suggests crosstalk between nataxazole and coelibactin pathways. Overproduction of UK-1 was obtained by growing a nataxazole non-producing mutant (lacking 6-methylsalicylate synthase, NatPK) in a zinc-deficient medium. Furthermore, Streptomyces sp. Tü 6176 also produces the siderophore enterobactin in an iron-free medium. Enterobactin production can be induced in an iron-independent manner by inactivating natAN, which encodes an anthranilate synthase involved in nataxazole production. The results indicate a close relationship between nataxazole, enterobactin and coelibactin pathways through the shikimate pathway, the source of their common precursor, chorismate.
authors.affiliation: Departamento de Biología Funcional, Instituto Universitario de Oncología del Principado de Asturias (I.U.O.P.A), Universidad de Oviedo, C/ Julian Clavería, s/n, 33006 Oviedo (Spain).
authors.forename: Carolina
authors.initials: C
authors.lastname: Cano-Prieto
authors.affiliation: Departamento de Biología Funcional, Instituto Universitario de Oncología del Principado de Asturias (I.U.O.P.A), Universidad de Oviedo, C/ Julian Clavería, s/n, 33006 Oviedo (Spain).
authors.forename: Armando A
authors.initials: AA
authors.lastname: Losada
authors.affiliation: Departamento de Biología Funcional, Instituto Universitario de Oncología del Principado de Asturias (I.U.O.P.A), Universidad de Oviedo, C/ Julian Clavería, s/n, 33006 Oviedo (Spain).
authors.forename: Alfredo F
authors.initials: AF
authors.lastname: Braña
authors.affiliation: Departamento de Biología Funcional, Instituto Universitario de Oncología del Principado de Asturias (I.U.O.P.A), Universidad de Oviedo, C/ Julian Clavería, s/n, 33006 Oviedo (Spain).
authors.forename: Carmen
authors.initials: C
authors.lastname: Méndez
authors.affiliation: Departamento de Biología Funcional, Instituto Universitario de Oncología del Principado de Asturias (I.U.O.P.A), Universidad de Oviedo, C/ Julian Clavería, s/n, 33006 Oviedo (Spain).
authors.forename: José A
authors.initials: JA
authors.lastname: Salas
authors.affiliation: Departamento de Biología Funcional, Instituto Universitario de Oncología del Principado de Asturias (I.U.O.P.A), Universidad de Oviedo, C/ Julian Clavería, s/n, 33006 Oviedo (Spain).
authors.forename: Carlos
authors.initials: C
authors.lastname: Olano
keywords: antibiotics; benzoxazoles; chorismate; coelibactin; enterobactin; natural products