Evolving enzyme technology for pharmaceutical applications: case studies

The case studies focus on two types of enzyme applications for pharmaceutical development. Demethylmacrocin O-methyltransferase, macrocin O-methyltransferase (both putatively rate-limiting) and tylosin reductase were purified from Streptomyces fradiae, characterized and the genes manipulated for inc...

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Bibliographic Details
Published in:Journal of industrial microbiology & biotechnology 1997-11, Vol.19 (5-6), p.334-343
Main Author: Yeh, W K
Format: Article
Language:English
Subjects:
Acremonium
Actinoplanes
Anti-Bacterial Agents - biosynthesis
Biotechnology
Cephalosporins - biosynthesis
Cephalosporium acremonium
Escherichia coli
Penicillium chrysogenum
Streptomyces clavuligerus
Streptomyces fradiae
Tylosin - biosynthesis
Xanthobacter
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Summary:The case studies focus on two types of enzyme applications for pharmaceutical development. Demethylmacrocin O-methyltransferase, macrocin O-methyltransferase (both putatively rate-limiting) and tylosin reductase were purified from Streptomyces fradiae, characterized and the genes manipulated for increasing tylosin biosynthesis in S. fradiae. The rate-limiting enzyme, deacetoxycephalosporin C (DAOC) synthase/hydroxylase (expandase/ hydroxylase), was purified from Cephalosporium acremonium, its gene over-expressed, and cephalosporin C biosynthesis improved in C. acremonium. Also, heterologous expression of penicillin N epimerase and DAOC synthase (expandase) genes of Streptomyces clavuligerus in Penicillium chrysogenum permitted DAOC production in the fungal strain. Second, serine hydroxymethyltransferase of Escherichia coli and phthalyl amidase of Xanthobacter agilis were employed in chemo-enzymatic synthesis of carbacephem. Similarly, echinocandin B deacylase of Actinoplanes utahensis was used in the second-type synthesis of the ECB antifungal agent.
ISSN:1367-5435
1476-5535
DOI:10.1038/sj.jim.2900437