Procedure for obtaining non-ribosomal peptides by heterologous expression of at least one non-ribosomal peptide synthetase in Aspergillus niger

摘要

Method of obtaining at least one non-ribosomal peptide, (NRP), or one isotopically labeled, the method comprising the heterologous expression step of at least one non-ribosomal peptide synthetase (NRPS) of said non-ribosomal peptide in the Aspergillus filamentous fungus niger, in which NRP synthetase is a cyclodepsipeptide synthetase selected from the group containing Enniatin, PF1022, Beauvericin and Bassianolide synthetase, in which an inducible expression system integrated into the genome of the filamentous fungus Aspergillus niger is used for expression heterologous of the at least one synthetase, wherein the expression system comprises at least one expression cassette comprising a first module for constitutive expression of the tetracycline-dependent rtTA2 trans-activator, a second module that houses the rtTA2-dependent promoter for inducible expression of the at least one secondary synthetase of a metabolite and a third module for the integration of the cassette into the fungal genome by homologous or heterologous recombination using appropriate selection markers.