METHOD FOR THE ANNOTATION OF NATURAL PRODUCT GENE-CLUSTERS AND FOR THE GENERATION OF NOVEL BIOLOGICALLY ACTIVE CHEMICAL ENTITIES FROM DNA SEQUENCES IN SILICO

摘要

The invention covers the generation of novel modular polyketide, non-ribosomal peptide, siderophore, hybrid and other modular biosynthetic pathway gene-clusters by the rapid in silico semiautomatic annotation of modular biosynthetic gene-clusters starting from DNA sequences and by the homologous recombination of the annotated gene-clusters in silico. This is achieved by: (1) acquisition, annotation, structuring, storage and graphical presentations of data, (2) precise prediction of activities and specificities of modular biosynthetic pathway domains, (3) modelling of biosynthetic processes, (4) modelling of starter and extender building blocks, (5) modelling of the translation of DNA sequences into the linear polyketide, peptide, siderophore, hybrid and other modular biosynthetic pathways chains, as well as modelling of the spontaneous ring formation from the predicted linear products of the recombinant gene-clusters. The invention allows the generation of a custom library of entirely novel chemical entities obtained by the in silico homologous recombination of modular biosynthetic gene-gene-clusters that can be used for the in silico screening of the potential biological activity using CDD technology.