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Mar Drugs ; 18(12)2020 Dec 11.
Article in English | MEDLINE | ID: mdl-33322429

ABSTRACT

A putative Type III Polyketide synthase (PKSIII) encoding gene was identified from a marine yeast, Naganishia uzbekistanensis strain Mo29 (UBOCC-A-208024) (formerly named as Cryptococcus sp.) isolated from deep-sea hydrothermal vents. This gene is part of a distinct phylogenetic branch compared to all known terrestrial fungal sequences. This new gene encodes a C-terminus extension of 74 amino acids compared to other known PKSIII proteins like Neurospora crassa. Full-length and reduced versions of this PKSIII were successfully cloned and overexpressed in a bacterial host, Escherichia coli BL21 (DE3). Both proteins showed the same activity, suggesting that additional amino acid residues at the C-terminus are probably not required for biochemical functions. We demonstrated by LC-ESI-MS/MS that these two recombinant PKSIII proteins could only produce tri- and tetraketide pyrones and alkylresorcinols using only long fatty acid chain from C8 to C16 acyl-CoAs as starter units, in presence of malonyl-CoA. In addition, we showed that some of these molecules exhibit cytotoxic activities against several cancer cell lines.


Subject(s)
Antineoplastic Agents/metabolism , Basidiomycota/enzymology , Fungal Proteins/metabolism , Polyketide Synthases/metabolism , Polyketides/metabolism , Antineoplastic Agents/pharmacology , Caco-2 Cells , Cell Survival/drug effects , Fungal Proteins/isolation & purification , Fungal Proteins/pharmacology , Humans , Hydrothermal Vents/microbiology , Neoplasms/drug therapy , Neoplasms/pathology , Phylogeny , Polyketide Synthases/isolation & purification , Polyketide Synthases/pharmacology , Polyketides/pharmacology , Substrate Specificity , THP-1 Cells , Water Microbiology
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