title: Expanding the Chemical Repertoire of the Endophyte Streptomyces albospinus RLe7 Reveals Amphotericin B as an Inducer of a Fungal Phenotype.
abstract: During an investigation of the chemistry of the endophytic actinobacterium Streptomyces albospinus RLe7, which was isolated from the roots of the Brazilian medicinal plant Lychnophora ericoides, three new natural products, (2R*,4S*)-2-((1'S*)-hydroxy-4'-methylpentyl)-4-(hydroxymethyl)butanolide (1), (3R*,4S*,5R*,6S*)-tetrahydro-4-hydroxy-3,5,6-trimethyl-2-pyranone (2), and 1-O-(phenylacetyl)glycerol (3), together with known secondary metabolites (S)-4-benzyl-3-oxo-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-6-carbaldehyde (4), (S)-4-isobutyl-3-oxo-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-6-carbaldehyde (5), and the diketopiperazines cyclo(l-Tyr-l-Pro) (6) and cyclo(l-Val-l-Pro) (7), were isolated. The role of isolated natural products in the interaction between S. albospinus RLe7 and the fungus Coniochaeta sp. FLe4, an endophyte from the same plant, was investigated. None of these isolated actinobacterial compounds were able to inhibit the fungus or induce the fungal red pigmentation observed when both endophytes interact. Further investigation using mass spectrometry approaches enabled identifying the well-known antifungal compound amphotericin B (9) as a microbial metabolite of S. albospinus RLe7. Finally, compound 9 was demonstrated as at least one of the agents responsible for both the antifungal activity and induction of red-pigmented fungal phenotype.
authors.affiliation: Departamento de Ciências Farmacêuticas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo , Avenida do Café, s/n, Ribeirão Preto, SP 14040-903, Brazil.
authors.forename: Fernanda Oliveira
authors.initials: FO
authors.lastname: Chagas
authors.affiliation: Departamento de Ciências Farmacêuticas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo , Avenida do Café, s/n, Ribeirão Preto, SP 14040-903, Brazil.
authors.forename: Andrés Mauricio
authors.initials: AM
authors.lastname: Caraballo-Rodríguez
authors.affiliation: Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego , 9500 Gilman Drive, La Jolla, California 92093-0751, United States.
authors.forename: Pieter C
authors.initials: PC
authors.lastname: Dorrestein
authors.affiliation: Departamento de Ciências Farmacêuticas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo , Avenida do Café, s/n, Ribeirão Preto, SP 14040-903, Brazil.
authors.forename: Mônica Tallarico
authors.identifier: 0000-0003-2705-0123
authors.initials: MT
authors.lastname: Pupo
mesh_terms: D000666:Amphotericin B / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D000935:Antifungal Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D001203:Ascomycota / Q000187:drug effects*; D019659:Asteraceae / Q000187:drug effects*; D001688:Biological Products / Q000737:chemistry / Q000378:metabolism*; D001938:Brazil; D054659:Diketopiperazines / Q000737:chemistry / Q000494:pharmacology*; D060026:Endophytes / Q000737:chemistry*; D015394:Molecular Structure; D018517:Plant Roots / Q000737:chemistry / Q000382:microbiology*; D013302:Streptomyces / Q000737:chemistry*
chemical_list: D000935:Antifungal Agents; D001688:Biological Products; D054659:Diketopiperazines; D000666:Amphotericin B