Molecular genetics of antibiotics biosynthesis

Course Description

COURSE CONTENT

Overview of antibiotic substances. Biology of bacterial genus Streptomyces – antibiotic producer, covering life cycle, process and biosynthesis of secondary metabolites. Traditional genetics of antibiotic synthesis in Streptomyces genus. Cloning of Streptomyces genes whose products are involved in antibiotic biosynthesis. Polyketide antibiotics. Origins, biological importance and chemical structures of antibioticaly active substances from polyketide class. Molecular mechanism of polyketide biosynthesis. Spatial organization of genes coding for polyketide synthases. Genetics of simple aromatic polyketide antibiotics. Molecular genetics of oxytetracyclin biosynthesis as example. Genetics of complex polyketide antibiotics. Molecular genetics of erythromycin A biosynthesis as example. Introduction to new “hybrid” antibiotics. New “hybrid” substances obtained using genetic engineering methods: (a) pre-condensation modifications of carbon backbone, (b) Post-condensation modifications of carbon backbone. Molecular biology and genetics of non ribosomaly synthesized peptides. Molecular genetics of penicillin G  biosynthesis as example. Conclusions and perspectives

LEARNING OUTCOMES

• Classify antibiotics and using erythromycin polyketide synthase explain molecular mechanism of polyketide biosynthesis
• Based on organization and annotation of modular polyketide synthase predict synthesized product.
• Identify regions in gene clusters which can be manipulated using genetic engineering methods to obtain new compounds.
• Critically think about antibiotic usage and trends in the society and to propagate responsible usage of antibiotics with general public.

Lectures

Lectures: 10 hours

Seminars: 10 hours

Literature

1. Kumar, P., Khosla, C., Tang, Y. Manipulation and analysis of polyketide synthases. Methods Enzymol.,  388: 269-293, 2004.
2. Finking, R., Marahiel, M.A.Biosynthesis of nonribosomal peptides1. Ann . Rev . Microbiol.,  58:453- 488, 2004.
3. Bentley, S.D., Chater, K.F., Cerdeno-Tarraga i sur. Complete genome sequence of the model actinomycete Streptomyces coelicolor A3(2). Nature,  417: 141-147, 2002.
4. Ikeda, H., Ishikawa, J., Hanamoto, A., Shinose, M., Kikuchi, H., Shiba, T., Sakaki, Y., Hattori, M., Omura, S. Complete genome sequence and comparative analysis of the industrial microorganism Streptomyces avermitilis. Nat. Biotechnol,  21: 526-531, 2003.