Bioconversion of indene to cis (1S,2R) indandiol and trans (1R,2R) indandiol by Rhodococcus species

cis (1S, 2R) indandiol or trans (1R,2R) indandiol are both potential precur sors to (-)-cis (1S,2R)-1-aminoindan-2-ol, a key chiral synthon for Crixiva n(R) (Indinavir), a leading HIV protease inhibitor. Enrichment and isolatio n studies yielded two Rhodococcus sp. strain B 264-1 (MB 5655) and strain I -24 (MA 7205) capable of biotransforming indene to cis (1S,2R) indandiol an d trans (IR,2R) indandiol respectively. Isolate MB 5655 was found to have a toluene dioxygenase, while isolate MA 7205 was found to harbor both toluen e and naphthalene dioxygenases as well as a naphthalene monoxygenase. When scaled up in a 14-l bioreactor, MB 5655 produced up to 2.0 g/l of cis (1S,2 R) indandiol with an enantiomeric excess greater than 99%. MA 7205 cultivat ed under similar conditions produced up to 1.4 g/l of trans (1R,2R) indandi ol with an enantiomeric excess greater than 98%. Process development studie s yielded titers greater that 4.0 g/l of cis indandiol for MB 5655. Due to their resistance to indene toxicity and easy cultivation in bioreactors, bo th Rhodococcus sp. strains appeared as good candidates for future strain en gineering and process development work.