The discovery of nature's biosynthetic pathways

Summary Uro'gen-III is a key intermediate on the biosynthetic pathways to the vitally important natural pigments haem, chlorophyll and the cytochromes. How the unexpected structure of uro'gen-III is synthesized by living things has long been a major puzzle. Studies based on¹³C-labelling are described which show a) that a single intramolecular rearrangement occurs and b) that this step occurs after the open-chain linear tetrapyrrole system has been built.A second study involves stereospecific labelling with deuterium and tritium to elucidate the absolute stereochemistry of the enzymic reaction sequence which produces the vinyl groups of haem. The third and last section of the lecture is focussed on the biosynthetic intermediates lying between uro'gen-III and cobyrinic acid on the pathway to vitamin B₁₂. An octacarboxylic isobacteriochlorin is isolated from a vitamin B₁₂-producing organism and this is shown to be identical with sirohydrochlorin, previously obtained by Kamin and Siegel as the metal-free prosthetic group of certain sulphite-reducing bacteria. The structure and absolute stereochemistry of sirohydrochlorin are studied and comment is made on the evolutionary interest of these findings.This account is a slightly extended version of the Paul Karrer Lecture given on July 5th, 1977 at the University of Zürich.