Industrial Biotransformations

d-Amino acid oxidase
Trigonopsis variabilis ATCC 10679
4) Process parameters
yield: Maximum 50 %
optical purity > 99 %
reactor type: batch
enzyme activity: 2 g washed cells per mL
company: Bristol-Myers Squibb, USA
5) Product application
● l-6-Hydroxynorleucine is a chiral intermediate useful for the synthesis of a vasopeptidase inhibitor
now in clinical trials and for the synthesis of C-7 substituted azepinones as potential
intermediates for other antihypertensive metalloproteinase inhibitors.
● 2-Keto-6-hydroxyhexanoic acid is converted further into l-6-hydroxynorleucine using amino
acid dehydrogenase and beef liver glutamate dehydrogenase.
6) Literature
EC 1.4.3.3
● Patel, R.N. (2001) Enzymatic synthesis of chiral intermediates for Omapatrilat, an antihypertensive
drug, Biomol. Eng. 17, 167-182
● Patel, R.N. (2001) Biocatalytic synthesis of intermediates for the synthesis of chiral drug substances,
Curr. Opin. Biotechnol. 12, (6) 587-604
● Patel, R.N. (2001) Enzymatic synthesis of chiral intermediates for drug development, Adv.
Synth. Catal. 343, (6-7) 527-546
● Hanson, L.R., Schwinden, D.M., Banerjee, A., Brzozowski, D.B., Chen, B.-C., Patel, B.P.,
McNamee, C.G., Kodersha, G.A., Kronenthal, D.R., Patel, R.N., Szarka, L.J. (1999) Enzymatic
synthesis of l-6-hydroxynorleucine, Bioorg. Med. Chem. 7, 2247–2252
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