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

被引：50

作者：

Chartrain, M ^{[1
]}

Jackey, B ^{[1
]}

Taylor, C ^{[1
]}

Sandford, V ^{[1
]}

Gbewonyo, K ^{[1
]}

Lister, L ^{[1
]}

Dimichele, L ^{[1
]}

Hirsch, C ^{[1
]}

Heimbuch, B ^{[1
]}

Maxwell, C ^{[1
]}

Pascoe, D ^{[1
]}

Buckland, B ^{[1
]}

Greasham, R ^{[1
]}

机构：

[1] Merck Res Labs, Rahway, NJ 07065 USA

来源：

JOURNAL OF FERMENTATION AND BIOENGINEERING | 1998年 / 86卷 / 06期

关键词：

biotransformation; bioconversion; biocatalysis; indene; indandiol; Crixivan (R); Indinavir; Rhodococcus;

D O I：

10.1016/S0922-338X(99)80005-1

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

cis (1S, 2R) indandiol or trans (1R,2R) indandiol are both potential precursors to (-)-cis (1S,2R)-1-aminoindan-2-ol, a key chiral synthon for Crixivan(R) (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 (1S,2R) indandiol and trans (IR,2R) 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 monoxygenase. When scaled up in a 14-l bioreactor, MB 5655 produced up to 2.0 g/l of cis (1S,2R) indandiol with an enantiomeric excess greater than 99%. MA 7205 cultivated under similar conditions produced up to 1.4 g/l of trans (1R,2R) 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.

引用

页码：550 / 558

页数：9

共 30 条

[1] Metabolism of naphthalene, 1-naphthol, indene, and indole by Rhodococcus sp strain NCIMB 12038 [J].