BIOSYNTHESIS OF PORPHYRIN COMPOUNDS

                      Tetrapyrroles play important roles in electron transport                        systems and function as prosthetic groups of many enzymes.                        Because of their importance to all living systems and their                        intense coloring, they have also been named the "pigments of life". These compounds have long been of interest for biomedical applications and drugs have been or are currently developed for e.g. cancer treatment, treatment of viruses, gene regulation therapies and more recently, drug targeting. Porphyrins, which absorb light at longer wavelengths, are of particular interest for biomedical laser applications such as photodynamic cancer treatment. Metalloporphyrins find innovative applications in electro-catalysis, as electrodes in fuel cells, as chemical sensors or as conductive materials. Chemical synthesis of many functionalized porphyrin structures is difficult; a biosynthetic approach, however, could synthesize novel porphyrin structures in good yields.

Our research in this area focuses on developing new biosynthetic routes to natural and unnatural porphyrin systems and on the investigation of the involved enzyme functions. We recently demonstrated that assembly of heterologous porphyrin biosynthetic genes in E. coli allows synthesis of a variety of tetrapyrrole structures in high yields. In addition, we developed a novel efficient high-throughput in vivo screen for the in vitro evolution of porphyrin metal chelatases, allowing the identification of novel structural determinants of chelatase activity. Extension of the recombinant heme pathways with genes involved in other porphyrin biosynthetic routes (siroheme, vitamin B12, chlorophyll) demonstrated new catalytic promiscuities of enzymes; allowing the biosynthesis of diverse porphyrin structures.

 

 

  

 

Last updated: November 2005
Copyright © 2005 by the Regents of the University of Minnesota

Biosynthetic routes to different tetrapyrrole classes investigated in recombinant E. coli. Microplate in the center shows production of various tetrapyrrole compounds by E. coli cells overexpressing different assembled tetrapyrrole pathways.