Bacterial production of trans-dihydroxycyclohexadiene carboxylates by metabolic pathway engineering

Abstract

Homochiral-cis-cyclohexa-3,5-diene-1,2-diols are important synthons. We found a way to produce trans-configured homochiral diols using recombinant Klebsiella pneumoniae 62-1. Transformation of this mutant (Phe- Trp- Tyr-) with plasmids carrying genes involved in chorismic and isochorismic acid metabolism leads to the production of either (+)-trans-(2S,3S)-2,3-dihydroxycyclohexa-4,6-dienecarboxylic acid or (-)-trans-(3R,4R)-3,4-dihydroxycyclohexa-1,5-dienecarboxylic acid, with a yield of 70 or 90 mg (l culture broth)−1, respectively. The metabolic shift from one diene to the other is caused by a change in activity of isochorismate hydroxymutase and/or isochorismatase which in turn results from growth under iron deficiency or overexpression of genes (entC and/or entB) involved in chorismate metabolism.