Discovery of dual PKS involved in sclerotiorin biosynthesis in Penicillium meliponae using genome mining and gene knockout.

Autor: Sousa TF; Grupo de Pesquisas em Metabolômica e Espectrometria de Massas, Universidade do Estado do Amazonas, Manaus, 690065-130, Brazil.; Embrapa Amazônia Ocidental, Manaus, 69010-970, Brazil.; Laboratório de Genética Molecular e de Microrganismos, Universidade Federal de Viçosa, Viçosa, 36570-900, Brazil., de Araújo Júnior MB; Grupo de Pesquisas em Metabolômica e Espectrometria de Massas, Universidade do Estado do Amazonas, Manaus, 690065-130, Brazil.; Instituto de Ciências Exatas e Tecnologia, Universidade Federal do Amazonas, Itacoatiara, 69103-128, Brazil., Peres EG; Grupo de Pesquisas em Metabolômica e Espectrometria de Massas, Universidade do Estado do Amazonas, Manaus, 690065-130, Brazil.; Departamento de Química, Universidade Federal do Amazonas, Manaus, 69067-005, Brazil., Souza MP; Departamento de Química, Universidade Federal do Amazonas, Manaus, 69067-005, Brazil., da Silva FMA; Departamento de Química, Universidade Federal do Amazonas, Manaus, 69067-005, Brazil., de Medeiros LS; Instituto de Ciências Ambientais Químicas e Farmacêuticas, Universidade Federal de São Paulo, Diadema, 09972-270, Brazil., de Souza ADL; Departamento de Química, Universidade Federal do Amazonas, Manaus, 69067-005, Brazil., de Souza AQL; Faculdade de Ciências Agrárias, Universidade Federal do Amazonas, Manaus, 69067-005, Brazil., Yamagishi MEB; Embrapa Agricultura Digital, Campinas, 13083-970, Brazil., da Silva GF; Embrapa Amazônia Ocidental, Manaus, 69010-970, Brazil., Koolen HHF; Grupo de Pesquisas em Metabolômica e Espectrometria de Massas, Universidade do Estado do Amazonas, Manaus, 690065-130, Brazil., De Queiroz MV; Laboratório de Genética Molecular e de Microrganismos, Universidade Federal de Viçosa, Viçosa, 36570-900, Brazil. mvqueiro@ufv.br.
Jazyk: angličtina
Zdroj: Archives of microbiology [Arch Microbiol] 2023 Jan 28; Vol. 205 (2), pp. 75. Date of Electronic Publication: 2023 Jan 28.
DOI: 10.1007/s00203-023-03414-1
Abstrakt: Fungi of the genus Penicillium section Sclerotiora have as their main characteristic the presence of orange-pigmented mycelium, which is associated with sclerotiorin, a chlorinated secondary metabolite of the azaphilone subclass of polyketides. Sclerotiorin presents anti-diabetes, antioxidant, anti-inflammatory, anti-Alzheimer, antiviral, and antimicrobial activities, which has always attracted the attention of researchers worldwide. During our ongoing search for azaphilone-producing Amazonian fungi, the strain of Penicillium MMSRG-058 was isolated as an endophyte from the roots of Duguetia stelechantha and showed great capacity for producing sclerotiorin-like metabolites. Using multilocus phylogeny, this strain was identified as Penicillium meliponae. Moreover, based on the genome mining of this strain through the reverse approach, a cluster of putative biosynthetic genes (BGC) responsible for the biosynthesis of sclerotiorin-like metabolites (scl cluster) was identified. The knockout of the sclA (highly reducing PKS) and sclI (non-reducing PKS) genes resulted in mutants with loss of mycelial pigmentation and terminated the biosynthesis of sclerotiorin-like metabolites: geumsanol B, chlorogeumsanol B, 7-deacetylisochromophilone VI, isochromophilone VI, ochrephilone, isorotiorin, and sclerotiorin. Based on these results, a biosynthetic pathway was proposed considering the homology of BGC scl genes with the azaphilone BGCs that have already been functionally characterized.
(© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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