Biotransformation of protriptyline by filamentous fungi and yeasts.
1. The potential of various fungi to metabolize protriptyline (an extensively used antidepressant) was studied to investigate similarities between mammalian and microbial metabolism. 2. Metabolites produced by each organism were isolated by high-pressure liquid chromatography and identified by nuclear magnetic resonance and mass spectrometry. The metabolites identified in one or more fungi were 2-hydroxyprotriptyline, N-desmethylprotriptyline, N-acetylprotriptyline, N-acetoxyprotriptyline, 14-oxo-N-desmethylprotriptyline, 2-hydroxy-acetoxyprotriptyline and 3-(5-hydrodibenzo[bf][7]annulen-5-yl)propanoic acid. 3. Among 27 filamentous fungi and yeast species screened, Fusarium oxysporum f. sp. pini 2380 metabolized 97% of the protriptyline added. Several other fungi screened gave significant metabolism of protriptyline, including Cunninghamella echinulata ATCC 42616 (67%), C. elegans ATCC 9245 (17%), C. elegans ATCC 36112 (22%), C. phaeospora ATCC 22110 (50%), F. moniliforme MRC-826 (33%) and F. solani 3179 (12%). 4. F. oxysporum f. sp. pini produced phase I and phase II metabolites and thus is a suitable microbial model for protriptyline metabolism.
Duhart
B T
BT
Division of Microbiology, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR 72079, USA.
Zhang
D
D
Deck
J
J
Freeman
J P
JP
Cerniglia
C E
CE
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism / Q000493:pharmacokinetics*; D001711:Biotransformation; D017173:Caenorhabditis elegans / Q000378:metabolism; D002175:Candida / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D005658:Fungi / Q000378:metabolism*; D005670:Fusarium / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D011530:Protriptyline / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*; D015003:Yeasts / Q000378:metabolism*
D000929:Antidepressive Agents, Tricyclic; D011530:Protriptyline