Isocitric acid from fermentation of sunflower oil - a new building
block for pharma?
The citric acid cycle, one of
the most important metabolic processes in our bodies, was formulated in
1937. Since then, all of the intermediates have been produced in
multigram quantities - with one exception,
(2R,3S)-isocitric acid. Athanassios Giannis and his team at the
University of Leipzig have finally done it. As they report in the
journal Angewandte Chemie, their process, a combination of one
biotechnological and one chemical step, starts with sunflower oil, a
renewable starting material. Isocitric acid and its derivatives thus
become accessible on a kilogram scale.
In the citric acid cycle, acetyl CoA, formed
in the breakdown of lipids, sugars, and amino acids, is used to
produce energy that is biochemically available to an organism. Carbon
dioxide and water are produced in this process. This reaction
mechanism is named after one of the intermediate products, the anion
of citric acid.
In nature, isocitric acid is always found with its isomer, citric acid.
The difference between these two compounds is merely that the hydroxy
group (-OH) is bound to a different carbon atom of each molecule.
Large-scale separation of the two isomers has not been possible. A
fermentative synthesis of the pure compound has also not worked.
Giannis team has now finally done it, thanks to a host of tiny helpers,
the yeast Yarrowia lipolytica, which produces isocitrate from refined
sunflower oil in previously unachievable yield and in a favorable
isocitrate to citrate ratio. After the biomass is filtered out,
electrodialysis is used to obtain the pure acids. The researchers use
a trick to separate citric acid from isocitric acid: They use methanol
to convert the compounds into the corresponding methyl esters. Why
does this work? Whereas the citric acid ester crystallizes, the
isocitric acid ester is a liquid. Separation then becomes child�s play.
Why was isocitric acid so important to these researchers? Isocitric
acid is a compound with chiral centers - carbon
atoms with four different groups bound to them. There are always two
versions of a chiral center, one being the mirror image of the other.
Smaller, easily accessible chiral compounds are useful building blocks
for the synthesis of complex natural products and are interesting
starting materials for the pharmaceutical industry. Isocitric acid
makes available a new assortment of such chiral building blocks.
Further Information
and Source:
-
Philipp Heretsch, Franziska Thomas, Andreas Aurich, Dr., Harald Krautscheid, Prof. Dr., Dieter Sicker, Prof. Dr., Athanassios
Giannis, Prof. Dr.: Synthesen mit einem chiralen Baustein aus dem Citratzyklus:
(2R,3S)-Isocitronens�ure aus einer Fermentation mit Sonnenblumen�l.
In: Angewandte Chemie International Edition; Published Online: 31 Jan 2008;
doi: 10.1002/anie.200705000. [see also:
supporting information]
