10月21日“绿色制药前沿论坛”第二十四讲预告

    题  目：Diversity and sources of building blocks in the biosynthesis of industrially important secondary metabolites: Why is this an important issue for the pharmaceutical industry?

 

    主讲人：Prof. Dr. Hrvoje Petkovic 

 

    时  间：2016年10月21日（星期五）15:30-16:30

 

    地  点：朝晖校区新教1202

    

    讲座内容简介（Abstract）：

    Enzymes involved in the biosynthesis of primary and secondary metabolites often display relaxed specificity (promiscuity) towards structurally similar substrates, resulting in the production of structurally similar analogues often called shunt products. Relaxed specificity of enzymes can be utilised in drug development efforts, e.g. in the scope of biosynthetic engineering approaches. However, in the industrial production of primary and secondary metabolites, shunt metabolites represent impurities, which often cause significant burden during upstream and particularly downstream processes. Structurally complex secondary metabolites are often “assembled” from diverse building blocks (precursors) originating from diverse biosynthetic pathways. The biosynthesis of medically important immunosuppressant FK506 (tacrolimus) and its analogue FK520 by Streptomyces tsukubaensis, for example, demands simultaneous availability of at least 6 precursors from diverse metabolic pathways. Thus it is not surprising that a number of closely related structural analogues are synthesised during the biosynthetic process. During the last decade, we have intensively studied primary and secondary pathways involved in FK506 biosynthesis. We have identified pathways significantly contributing to the production of undesired impurities, demonstrating interaction of the primary and secondary pathways in FK506 biosynthesis by S. tsukubaensis, which has had significant impact on industrial strain and process development approaches. Manipulation of selected pathways using metabolic engineering resulted in the improved impurity profile of FK506 in the industrial setting.  

 

    主讲人简介：

    Dr. Hrvoje Petkovi'c holds a position of professor of microbial biotechnology at the Biotechnical Faculty, University of Ljubljana. He completed his PhD at University of Strathclyde (Glasgow, Scotland), followed by postdoctoral position at Biotica (Cambridge, UK). He has over 20 years experience in microbial biotechnology, metabolic and biosynthetic engineering and drug discovery. His expertise extends to the industrial strain improvement, process development, expertise in secondary metabolite gene regulation, and drug development mostly focused on actinomycetes hosts producing medically important drugs such as antibacterial tetracyclines and macrolides (erythromycin), immunosuppressant FK506 and anticancer rapamycin. He led research groups and developed industrial processes which have been implemented at industrial scale. Dr. Petkovi'c has been working for and collaborating with number of large pharmaceutical companies and specialized biotechnology companies such as chemical, biotechnology, food and pharmaceutical industry worldwide  (e.g. Lonza, Sandoz, GSK, Krka Pharmaceuticals, Ljubljanske mlekarne (Lactalis group), Galapagos, Biotica Ltd in Europe and  number of companies in China  (e.g. Acebright, Datong). Dr. Petkovi'c has led number of national, EU and industrially funded projects. He has extensive experience in project and IP management. He is co-inventor in number of EU and US granted patents and patent applications curtly being processed. Dr. Petkovi'c is teaching at Biotechnical Faculty, Study of Biotechnology and Microbiology, at undergraduate and postgraduate level, including subjects such as Microbial biotechnology, Bioprocessing, Technology of secondary metabolites, Metabolic engineering and Industrial biotechnology. He was mentor to 7 PhD students and is currently supervising two PhD student. He has supervised a number of MSc and BSC diploma work students. He has received a number of awards for academic and industrial achievements. He is author of a number of high-impact scientific publications and number of EU and USA granted patents.