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

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Sousa, Thiago F. F. ; de Araujo Junior, Moyses B. ; Peres, Eldrinei G. G. ; Souza, Mayane P. P. ; da Silva, Felipe M. A. ; de Medeiros, Livia S. ; de Souza, Afonso D. L. ; de Souza, Antonia Q. L. ; Yamagishi, Michel E. B. ; da Silva, Gilvan F. F. ; Koolen, Hector H. F. ; De Queiroz, Marisa V. V.

• Tipo de documento: Artigo Científico
• Fonte: Archives of Microbiology; v. 205, n. 2, p. 12-pg., 2023-02-01.

Resumo

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. (AU)

• Processo FAPESP: 20/08270-0 - Diversificação metabólica de fungos do gênero Penicillium isolados dos biomas Mata Atlântica e Amazônia: uma perspectiva para a produção de biomoléculas
• Beneficiário: Lívia Soman de Medeiros
• Modalidade de apoio: Auxílio à Pesquisa - Regular