ScienceDaily (Apr. 16, 2012) —
Chemists and biologists from the University of Bristol have finally
cracked one of the longest standing chemical mysteries. In a paper
published April 16 in Proceedings of the National Academy of Sciences, the team demonstrate exactly how an unusual class of compounds known as tropolones are synthesised in fungi.
In 1942, an 'unidentifiable' aromatic compound known as stipitatic
acid was first isolated from fungi. By 1945 the structure was solved but
it was so unique that it caused a revolution in the understanding of
Stipitatic acid is very unusual as it displays similar aromatic
properties to the six-membered rings in benzene-based compounds, but is a
seven-membered carbon ring known as a tropolone. New theoretical models
developed to understand tropolones now underpin our understanding of
structure and bonding in organic chemistry.
However it remained a mystery as to how fungi are able to synthesise such a product under biological conditions -- until now.
Using a combination of genetic and chemical methods, Dr Andy Bailey
and Professor Russell Cox and colleagues were able to identify the genes
responsible for this process, blocking the synthetic pathway at
different steps and thus demonstrating how, on a molecular scale, the
tropolone structure is produced. This is the core of a number of fungal
compounds including stipitatic acid, the xenovulenes which are
antidepressants and the antimalarial compound puberulic acid.
Knowledge of tropolone biosynthetic pathway is in itself very
interesting to chemists, but it may also lead to the discovery of new
Professor Cox of Bristol's School of Chemistry, who led the project,
said: "Members of this class of compound are well known as having
antibacterial properties and some have promise as antimalarial
treatments -- we now plan to engineer fungi to produce these new
It is hoped that identification of the enzymes responsible for
tropolone synthesis will help in generating a wider range of compounds
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- J. Davison, A. al Fahad, M. Cai, Z. Song, S. Y. Yehia, C. M. Lazarus, A. M. Bailey, T. J. Simpson, R. J. Cox. Genetic, molecular, and biochemical basis of fungal tropolone biosynthesis. Proceedings of the National Academy of Sciences, 2012; DOI: 10.1073/pnas.1201469109