Metabolic modeling of Streptomyces and its relatives: a constraints-based approach

PhD ceremony: Mr. M.T. Alam, 16.15 uur, Doopsgezinde Kerk, Oude Boteringestraat 33, Groningen

Dissertation: Metabolic modeling of Streptomyces and its relatives: a constraints-based approach

Promotor(s): prof. R. Breitling, prof. R.C. Jansen

Faculty: Mathematics and Natural Sciences

 

Taqeer Alam explored the metabolic system of two antibiotic producing model bacteria, Streptomyces coelicolor and Streptomyces clavuligerus, and computationally investigated their mechanism of antibiotic production.

Streptomyces species are often referred to as ‘antibiotic factories’ due to their ability to produce a large number of clinically important compounds. They belong to the order Actinomycetales, which is biologically very diverse of showing differences in genome size, pathogenicity, ecological niche, as well as in the ability of some of the species to produce various secondary metabolites.

Alams thesis starts by introducing the genus Streptomyces and its relatives and describing the modelling techniques used for analyzing their metabolic functions. To understand how these antibiotic producing species are phylogenetically related to other species of the group Actinomycetales, he constructed a comprehensive phylogenetic tree, and established a generally usable robust approach to construct fully resolved phylogenetic trees from genome sequences.

Results of the phylogenetic study formed the basis for large-scale metabolic modeling, and Alam identified metabolic as well as topological commonalities and differences among members of the group. Furthermore, by combining phylogenetic information with gene expression data he prioritized ‘orphan’ genes of Streptomyces coelicolor for future experimental study. Finally, the thesis concludes by discussing the future use of his results and models and outlines some perspective for further research into the system biology of antibiotic producing microbes.

The applied aspects of Alams results may be of general interest, in particular the fact that computers are becoming an essential tool for biologists, as they start engineering new life forms at an increasingly ambitious scale (‘synthetic biology’), e.g. to create bacteria that efficiently produce new antibiotics to combat the drug-resistant bacteria that are rapidly becoming a serious public health threat, especially in hospitals.