title: Metabolic fate of 3α,5-cycloandrostanes in the endogenous lactonization pathway of Aspergillus tamarii KITA.
abstract: A series of 3α,5-cycloandrostane analogues with a range of functionality (6α and 6β alcohols and ketone) at carbon 6 were tested in the endogenous lactonization pathway in Aspergillus tamarii KITA. This metabolic route converts progesterone to testololactone in high yield through a four step enzymatic pathway. To date, no studies have looked at the effect of steroids devoid of polar functionality at carbon 3 and their subsequent metabolic fate by fungi which contain Baeyer-Villiger monooxygenases. Incubation of all of the cycloandrostane analogues resulted in lactonization of ring-D irrespective of C-6 stereochemistry or absence of C-3 functionality. Presence of 6β-hydroxy group and the C-17 ketone was required in order for these analogues to undergo hydroxylation at C-15β position. All metabolites were isolated by column chromatography and were identified by (1)H, (13)C NMR, DEPT analysis and other spectroscopic data.
authors.affiliation: Manchester Pharmacy School, University of Manchester, Stopford Building, Oxford Road, Manchester M13 9PT, United Kingdom. Electronic address: Christy.hunter@manchester.ac.uk.
authors.forename: A Christy
authors.initials: AC
authors.lastname: Hunter
authors.affiliation: University of Brighton, School of Pharmacy and Biomolecular Sciences, Huxley Building, Lewes Road, Brighton BN2 4GJ, United Kingdom.
authors.forename: Shreyal
authors.initials: S
authors.lastname: Patel
authors.affiliation: University of Brighton, School of Pharmacy and Biomolecular Sciences, Huxley Building, Lewes Road, Brighton BN2 4GJ, United Kingdom.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Dedi
authors.affiliation: University of Brighton, School of Pharmacy and Biomolecular Sciences, Huxley Building, Lewes Road, Brighton BN2 4GJ, United Kingdom.
authors.forename: Howard T
authors.initials: HT
authors.lastname: Dodd
authors.affiliation: Manchester Pharmacy School, University of Manchester, Stopford Building, Oxford Road, Manchester M13 9PT, United Kingdom.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Bryce
mesh_terms: D000731:Androstanes / Q000378:metabolism*; D001230:Aspergillus / Q000378:metabolism*; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D013329:Structure-Activity Relationship
chemical_list: D000731:Androstanes
keywords: 3α,5-Cyclosteroid; Aspergillus tamarii; Biocatalysis; Biotransformation; Hydroxylation; Lactonization