Biosynthesis as a model: Based on the branched structure of biosynthetic pathways, such as the shikimate pathway, the selective bioproduction of a set of diverse metabolites has been achieved by means of metabolic engineering (see scheme). A scale‐up for preparative purposes was performed, resulting in high product titers and yields from renewable resources.

Cyclohexadiene-trans-5,6-diols such as (S,S)-2,3-dihydroxy-2,3-dihydrobenzoic acid (2,3-trans-CHD) have been shown to be of importance as chiral starting materials for the syntheses of bioactive substances, especially for the syntheses of carbasugars. By using methods of metabolic-pathway engineering, the Escherichia coli genes entB and entC, which encode isochorismatase and isochorismate synthase, were cloned and over-expressed in E. coli strains with a deficiency of entA, which encodes 2,3-dihydroxybenzoate synthase. A 30-fold increase in the corresponding EntB/EntC enzyme activities affects the accumulation of 2,3-trans-CHD in the cultivation medium. Although the strains did not contain deletions in chorismate-utilising pathways towards aromatic amino acids, neither chorismate nor any other metabolic intermediates were found as by-products. Fermentation of these strains in a 30 L pH-controlled stirred tank reactor showed that 2,3-trans-CHD could be obtained in concentrations of up to 4.6 g L(-1). This demonstrates that post-chorismate metabolites are accessible on a preparative scale by using techniques of metabolic-pathway engineering. Isolation and separation from fermentation salts could be performed economically in one step through anion-exchange chromatography or, alternatively, by reactive extraction. Starting from 2,3-trans-CHD as an example, we established short syntheses towards new carbasugar derivatives.

A new synthesis of ent-senepoxide and iso-crotepoxide starting from microbially produced(+)-trans-2,3-dihydroxy-2,3-dihydrobenzoic acid via regio- and stereoselective epoxidation is described.

Biosynthese als Modell: Ausgehend von der verzweigten Struktur von Biosynthesewegen wie dem Shikimat‐Weg gelang die selektive Bioproduktion eines Satzes diverser Metaboliten durch metabolisches Engineering. Ansätze im präparativen Maßstab waren ebenfalls erfolgreich und lieferten hohe Produkttiter und ‐ausbeuten aus erneuerbaren Quellen.

Carboxylic acidsCarboxylic acids Q 0420 (S,S)-2,3-Dihydroxy-2,3-dihydrobenzoic Acid: Microbial Access with Engineered Cells of Escherichia coli and Application as Starting Material in Natural-Product Synthesis. -An efficient microbial synthesis of the title acid (II) is reported using methods of deregulating the metabolic flux in E. coli strains. (II) can easily be transformed into the enantiomer(V) of the plant-growth inhibitor streptol. -(FRANKE, D.; LORBACH, V.; ESSER, S.; DOSE, C.; SPRENGER, G. A.; HALFAR, M.; THOEMMES, J.; MUELLER, R.; TAKORS, R.; MUELLER*, M.; Chem. Eur. J. 9 (2003) 17, 4188-4196; Inst. Biotechnol., Forschungszent. Juelich GmbH, D-52425 Juelich, Germany; Eng.) -Jannicke 51-093