ISSN:
1476-5535
Keywords:
Lipase
;
Bioconversion
;
Biocatalysis
;
Leukotriene receptor antagonist
;
Verlukast
;
Screening
;
Pseudomonas aeruginosa
Source:
Springer Online Journal Archives 1860-2000
Topics:
Biology
,
Process Engineering, Biotechnology, Nutrition Technology
Notes:
Summary A search was implemented for a microbial lipase capable of bioconverting a diester (dimethyl 5-(3-(2-(7-chloroquinolin-2-yl)ethyl)phenyl)4,6-dithianon to its S-ester acid, an intermediate in the production of Verlukast (a leukotriene receptor antagonist). Required properties of the sought-after enzyme included a high enantiomeric selectivity (e.e. 〉98%), the formation of only trace amounts of diacid and a high bioconversion rate. This search yielded 57 lipase-producing microorganisms, 18 of which presented detectable bioconversion activity. Thirteen of these microbes were selected for further study based upon their lipase production level and enzyme stability at harvest. Despite their common enzymatic property, namely the hydrolysis of triglycerides, these lipase preparations presented diverse ester acid specific synthesis rates (from 〈0.01 μg/unit/h to 0.98 μg/unit/h) and diacid formation levels (from 0% to 35%). One of these microbes, identified asPseudomonas aeruginosa (strain MB 5001), was found to produce a lipase having all of the above-listed required properties. The initial fermentation process developed in shake flasks was rapidly and successfully scaled up in 23-liter labora bioreactors, achieving a maximum production of 35 units/ml of lipase after 48 h of cultivation.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF01583680
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