Related Experiment Video
Updated: May 9, 2026

From a Natural Product to Its Biosynthetic Gene Cluster: A Demonstration Using Polyketomycin from Streptomyces diastatochromogenes Tü6028
Published on: January 13, 2017
Engineering the biosynthesis of the polyketide-nonribosomal peptide collismycin A for generation of analogs with
Ignacio Garcia1, Natalia M Vior, Javier González-Sabín
1Departamento de Biología Funcional e Instituto Universitario de Oncología del Principado de Asturias, Universidad de Oviedo, 33006 Oviedo, Spain.
Abstract:
Collismycin A is a member of the 2,2'-bipyridyl family of natural products that shows cytotoxic activity. Structurally, it belongs to the hybrid polyketides-nonribosomal peptides. After the isolation and characterization of the collismycin A gene cluster, we have used the combination of two different approaches (insertional inactivation and biocatalysis) to increase structural diversity in this natural product class. Twelve collismycin analogs were generated with modifications in the second pyridine ring of collismycin A, thus potentially maintaining biologic activity. None of these analogs showed better cytotoxic activity than the parental collismycin. However, some analogs showed neuroprotective activity and one of them (collismycin H) showed better values for neuroprotection against oxidative stress in a zebrafish model than those of collismycin A. Interestingly, this analog also showed very poor cytotoxic activity, a feature very desirable for a neuroprotectant compound.
Related Concept Videos
Production of Pharmaceuticals
Production of Antibiotics
Biosynthesis in Bacteria
