Flexibility of the endogenous progesterone lactonisation pathway in Aspergillus tamarii KITA: transformation of a series of cortical steroid analogues.
A range of cortical steroids have been transformed by the fungus Aspergillus tamarii, which has the ability to convert progesterone to testololactone in high yield through a four step enzymatic pathway. 16alpha,17alpha-Epoxyprogesterone underwent a rare epoxide opening resulting in a unique inversion of stereochemistry to give 16beta-hydroxy-17alpha-oxa-D-homo-androst-4-en-3,17-dione. The metabolism of deoxycorticosterone resulted in relatively efficient transformation to testololactone with no other products isolated. Transformation of 17alpha-hydroxyprogesterone yielded 17alpha-oxa-D-homo-androst-1,4-dien-3,17-dione, a lactone not previously isolated from A. tamarii. Cortexolone was transformed to the 20(R)-alcohol with no further transformation observed. Evidence is also presented for the presence of a highly flexible but stereospecific keto-reductase. All metabolites were isolated by column chromatography and were identified by 1H, 13C NMR, DEPT analysis and other spectroscopic data.
Hunter
A Christy
AC
Molecular Targeting and Polymer Toxicology Group, School of Pharmacy and Biomolecular Sciences, University of Brighton, Brighton, BN2 4GJ East Sussex, UK. c.hunter@bton.ac.uk
Carragher
Natasha E
NE
D001230:Aspergillus / Q000235:genetics / Q000378:metabolism*; D003350:Cortodoxone / Q000737:chemistry / Q000378:metabolism*; D018360:Crystallography, X-Ray; D003900:Desoxycorticosterone / Q000737:chemistry / Q000378:metabolism*; D007783:Lactones / Q000737:chemistry / Q000378:metabolism*; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D011374:Progesterone / Q000031:analogs & derivatives / Q000378:metabolism*; D013237:Stereoisomerism
D007783:Lactones; D003900:Desoxycorticosterone; D011374:Progesterone; D003350:Cortodoxone