Abstract
BackgroundMetabolic activities of microorganisms to modify the chemical structures of organic compounds became an effective tool for the production of high-valued steroidal drugs or their precursors. Currently research efforts in production of steroids of pharmaceutical interest are focused on either optimization of existing processes or identification of novel potentially useful bioconversions. Previous studies demonstrated that P. lanosocoeruleum KCH 3012 metabolizes androstanes to the corresponding lactones with high yield. In order to explore more thoroughly the factors determining steroid metabolism by this organism, the current study was initiated to delineate the specificity of this fungus with respect to the cleavage of steroid side chain of progesterone and pregnenolone The effect of substituents at C-16 in 16-dehydropregnenolone, 16α,17α-epoxy-pregnenolone and 16α-methoxy-pregnenolone on the pattern of metabolic processing of these steroids was also investigated.Results and discussionAll of the analogues tested (except the last of the listed) in multi-step transformations underwent the Baeyer–Villiger oxidation to their δ-d-lactones. The activity of 3β-HSD was a factor affecting the composition of the product mixtures. 16α,17α-epoxy-pregnenolone underwent a rare epoxide opening with retention stereochemistry to give four 16α-hydroxy-lactones. Apart from oxidative transformations, a reductive pathway was revealed with the unique hydrogenation of 5-ene double bond leading to the formation of 3β,16α-dihydroxy-17a-oxa-d-homo-5α-androstan-17-one. 16α-Methoxy-pregnenolone was transformed to the 20(R)-alcohol with no further conversion.ConclusionsThis work clearly demonstrated that P. lanosocoeruleum KCH 3012 has great multi-functional catalytic properties towards the pregnane-type steroids. Studies have highlighted that a slight modification of the d-ring of substrates may control metabolic fate either into the lactonization or reductive and oxidative pathways. Possibility of epoxide opening by enzymes from this microorganism affords a unique opportunity for generation of novel bioactive steroids.
Highlights
Metabolic activities of microorganisms to modify the chemical structures of organic compounds became an effective tool for the production of high-valued steroidal drugs or their precursors
This work clearly demonstrated that P. lanosocoeruleum KCH 3012 has great multi-functional catalytic properties towards the pregnane-type steroids
This work and previous studies with P. lanosocoeruleum KCH 3012 clearly demonstrated that this microorganism has potent multi-functional catalytic properties towards androstane- and pregnane-type steroids
Summary
Metabolic activities of microorganisms to modify the chemical structures of organic compounds became an effective tool for the production of high-valued steroidal drugs or their precursors. In order to explore more thoroughly the factors determining steroid metabolism by this organism, the current study was initiated to delineate the specificity of this fungus with respect to the cleavage of steroid side chain of progesterone and pregnenolone The effect of substituents at C-16 in 16-dehydropregnenolone, 16α,17α-epoxy-pregnenolone and 16α-methoxy-pregnenolone on the pattern of metabolic processing of these steroids was investigated. Steroids are an important class of natural compounds, ubiquitous in nature and playing crucial functions for metabolism. Their physiological activity depends on the structure, primarily location and stereochemistry of the functional groups attached to the steroid nucleus. Baeyer– Villiger oxidation (BVO) became object of growing interest considering the fact that the result of this reactions can provide steroids with anticancer and anti-androgenic properties
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