PhD ceremony Mr. H. Ali: Nonribosomal peptide synthetases and secondary metabolite production in Penicillium chrysogenum

PhD ceremony: Mr. H. Ali, 16.15 uur, Academiegebouw, Broerstraat 5, Groningen

Dissertation: Nonribosomal peptide synthetases and secondary metabolite production in Penicillium chrysogenum

Promotor(s): prof. A.J.M. Driessen

Faculty: Mathematics and Natural Sciences

In his thesis Hazrat Ali reported three new secondary metabolite biosynthetic pathways with more than fifty secondary metabolites with important biological properties. These metabolites may be utilized for human benefits as they have antimicrobial, antibiotic, anti-cancer and neurotoxin properties The remarkable feature of all three biosynthetic pathways is the large number of intermediates and/or products that is the result of a distinct unspecificity of the NRPS and/or modifying enzymes involved. Through the use of highly sensitive detection techniques based on mass spectrometry, novel compounds with important biological activity could be detected that had not been seen before.

Overall, this demonstrates that P. chrysogenum has the capability to synthesize multiple metabolites at a time. We also observed that by the deletion of the biosynthetic roquefortine/meleagrine pathway resulted in increase in production of chrysogen and related metabolites and vice versa even though the expression of the genes involved remained unaltered. This phenomenon is likely due to a re-direction of the metabolic (nitrogen) flux yielding increased levels of particular metabolites. This implies that for an optimal P. chyrsogenum strain, it is desirable to inactivate all unnecessary secondary metabolite genes. Remarkably, this is a phenomenon that to some extent already happened during the classical strain improvement that resulted in the silencing or mutational inactivation of various secondary metabolite genes.