Ring expansion of 3-methylorcinaldehyde to give the tropolone ring. Image by R.J. Cox and A.M. Bailey |
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
organic chemistry.
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 drugs.
Professor
Russell 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
compounds.”
It
is hoped that identification of the enzymes responsible for tropolone
synthesis will help in generating a wider range of compounds for
evaluation.
Genetic, Molecular and Biochemical Basis of Fungal Tropolone Biosynthesis
Source: University of Bristol
