Biotransformation of metoprolol by the fungus Cunninghamella blakesleeana.
OBJECTIVE
To investigate the biotransformation of metoprolol, a beta1-cardioselective adrenoceptor antagonist, by filamentous fungus, and to compare the parallels between microbial transformation and mammalian metabolism.


METHODS
Five strains of Cunninghamella (C elegans AS 3.156, C elegans AS 3.2028, C echinulata AS 3.2004, C blakesleeana AS 3.153 and AS 3.910) were screened for the ability to transform metoprolol. The metabolites of metoprolol produced by C blakesleeana AS 3.153 were separated and assayed by liquid chromatography-tandem mass spectrometry (LC/MS(n)). The major metabolites were isolated by semipreparative HPLC and the structures were identified by a combination of LC/MS(n) and nuclear magnetic resonance analysis.


RESULTS
Metoprolol was transformed to 7 metabolites; 2 were identified as new metabolites and 5 were known metabolites in mammals.


CONCLUSIONS
The microbial transformation of metoprolol was similar to the metabolism in mammals. The fungi belonging to Cunninghamella species could be used as complementary models for predicting in vivo metabolism and producing quantities of metabolite references for drugs like metoprolol.
Ma
Bin
B
Center for Drug Metabolism and Pharmacokinetics Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Huang
Hai-hua
HH
Chen
Xiao-yan
XY
Sun
Yu-ming
YM
Lin
Li-hong
LH
Zhong
Da-fang
DF
D000319:Adrenergic beta-Antagonists / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D020093:Cunninghamella / Q000378:metabolism*; D006801:Humans; D013058:Mass Spectrometry; D008790:Metoprolol / Q000737:chemistry / Q000378:metabolism*; D015394:Molecular Structure
D000319:Adrenergic beta-Antagonists; D008790:Metoprolol