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Philipp Schwarzer

Philipp Schwarzer


Investigations on the biosynthesis of Rishirilide

Principal Investigator: Prof. Dr. Andreas Bechthold

 

 

Abstract

Rishirilides A and B are secondary metabolites produced by Streptomyces bottropensis (formerly Streptomyces sp. Gö C4/4). Rishirilide B is a potential α2-macroglobulin inhibitor and could be used for prevention and treatment of fibrinolytic induced thrombosis. The basic structure of the aromatic polyketide rishirilide B consists of three partially aromatic cycles with three side chains, which is exceptional for polyketides of this type. 

         
                                         

 


         Figure: Rishirilide B    

                                    
We try to elucidate the biosynthetic pathway of rishirilide B by inactivation and heterologous expression experiments of different genes from the rishirilide gen cluster.

In particular, we focus on the function of the four transporter genes in the gene cluster. RslT1, rslT2 and rslT3 encode an ABC transporter system, whereas rslT4 encodes a MFS multidrug transporter, which is most likely involved in the export of rishirilid in the periplasmic space. By structural and functional studies, we want to understand the precise function of these genes.

Methods

  • Molecular biology (e.g. cloning, gDNA isolation,...)
  • Gene expression and protein purification
  • Natural product purification: SPE, TLC, HPLC-MS