Engineering an indene bioconversion process for the production of cis-aminoindanol: a model system for the production of chiral synthons.
Cis-aminoindanol, a key chiral precursor to the HIV protease inhibitor CRIXIVAN, can be derived from indene oxidation products of (2R) stereochemistry. A number of different microorganisms, notably strains of the genera Pseudomonas and Rhodococcus, have been isolated that catalyze the oxygenation of indene to indandiol with greater stereospecificity than is achievable through traditional chemical synthesis. The yield and ultimate optical purity of indandiol produced in such biocatalytic processes is influenced by the intrinsic stereospecificity of the oxygenase(s), enantioselective dehydrogenation, and the loss of substrate to alternate, undesirable metabolites. Metabolic engineering of any indene bioconversion system for the commercial-scale production of cis-aminoindanol must account for these influences, as well as pathway fluxes and enzyme regulation, to optimize the formation of oxygenated precursors with useful stereochemistry. As such, the process by which bacterial systems carry out the bioconversion of indene to indandiol serves as a model for biological production of industrially relevant chiral synthons.
O'Brien
X M
XM
Department of Biology 68-370, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Parker
J A
JA
Lessard
P A
PA
Sinskey
A J
AJ
D001709:Biotechnology / Q000379:methods; D005818:Genetic Engineering / Q000379:methods*; D017320:HIV Protease Inhibitors / Q000737:chemistry / Q000378:metabolism; D007189:Indans / Q000378:metabolism*; D007192:Indenes / Q000378:metabolism*; D019469:Indinavir / Q000737:chemistry / Q000378:metabolism; D010105:Oxygenases / Q000235:genetics / Q000378:metabolism; D016958:Pseudomonas putida / Q000201:enzymology* / Q000235:genetics; D012240:Rhodococcus / Q000201:enzymology* / Q000235:genetics
D017320:HIV Protease Inhibitors; D007189:Indans; D007192:Indenes; C116915:aminoindanol; D019469:Indinavir; D010105:Oxygenases