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

• Published in: Journal of fermentation and bioengineering Vol. 86; no. 6; pp. 550 - 558
• Main Authors: Chartrain, Michel, Jackey, Barbara, Taylor, Colleen, Sandford, Vanessa, Gbewonyo, Kodzo, Lister, Leonard, Dimichele, Lisa, Hirsch, Charles, Heimbuch, Brian, Maxwell, Carrie, Pascoe, Deborah, Buckland, Barry, Greasham, Randolph
• Format: Journal Article
• Language: English
• Published: Osaka Elsevier B.V 01.01.1998; Society for Fermentation and Bioengineering
• Subjects: Bacteria; biocatalysis; Biocatalysts; BIOCONVERSION; Bioconversions. Hemisynthesis; Biological and medical sciences; Biotechnology; biotransformation; Crixivan; Drug products; DRUGS; Enzyme inhibition; Fundamental and applied biological sciences. Psychology; Human immunodeficiency virus; indandiol; indene; Indinavir; MEDICAMENT; MEDICAMENTOS; Methods. Procedures. Technologies; Rhodococcus; RHODOCOCCUS (BACTERIA); biotransformation; indene; bioconversion; Crixivan; Rhodococcus; indandiol; biocatalysis; Indinavir; Toluene dioxygenase; Diol; Enzyme; Retroviridae; Lentivirus; Precursor; Optimization; Cis stereoisomer; Virus; Stereoselectivity; Indene; Biotransformation; Trans stereoisomer; Production; Bacteria; Antiviral; Isolation; Actinomycetes; Oxidoreductases; Human immunodeficiency virus; Protease inhibitor; Naphthalene 1,2-dioxygenase
• ISSN: 0922-338X
• DOI: 10.1016/S0922-338X(99)80005-1

cis (1 S,2 R) indandiol or trans (1 R,2 R) indandiol are both potential precursors to (−)- cis (1 S,2 R)-1-aminoindan-2-ol, a key chiral synthon for Crixivan ® (Indinavir), a leading HIV protease inhibitor. Enrichment and isolation studies yielded two Rhodococcus sp. strain B 264-1 (MB 5655) and strain I-24 (MA 7205) capable of biotransforming indene to cis (1 S,2 R) indandiol and trans (1 R,2 R) indandiol respectively. Isolate MB 5655 was found to have a toluene dioxygenase, while isolate MA 7205 was found to harbor both toluene and naphthalene dioxygenases as well as a naphthalene monooxygenase. When scaled up in a 14- l bioreactor, MB 5655 produced up to 2.0 g/ l of cis (1 S,2 R) indandiol with an enantiometric excess greater than 99%. MA 7205 cultivated under similar conditions produced up to 1.4 g/ l of trans (1 R,2 R) indandiol with an enantiomeric excess greater than 98%. Process development studies 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, both Rhodococcus sp. strains appeared as good candidates for future strain engineering and process development work.