Enzymatic Baeyer–Villiger oxidation of steroids with cyclopentadecanone monooxygenase

Abstract

Recombinant cyclopentadecanone monooxygenase from Pseudomonas sp. catalyzed the preparative-scale Baeyer-Villiger oxidation of numerous 3 and 17-ketosteroids with a full control of the regiochemistry of the produced lactones. The recovered product yields were up to 42%.

Steroid Hydroxylation by Basidiomycete Peroxygenases: a Combined Experimental and Computational Study

“…Minor hydroxylation at the terminal positions of the steroid branched side chain by AaeUPO and MroUPO also leads in some cases (e.g., cholesterol) to formation of the C-26/C-27-carboxylated derivatives, in addition to the C-26/C-27-hydroxylated ones. This is because of the further oxidation (successive hydroxylation and dehydration reactions) of the monohydroxylated prod- ucts, as previously demonstrated in 18 O-labeling oxygenation studies with AaeUPO and H 2 18 O 2 (11). Hydroxylation at positions other than C-25 occurs in cases that show a high (energetically favorable) occupation of binding positions near any of these centers, as demonstrated for AaeUPO by computational studies.…”

“…The physiological activity of steroids depends on their structures, including the oxidation state of the rings, and the type, number, and regio-and stereoposition of the functional groups attached (1). It is known that even minor changes in the structure of steroids can highly affect their biological activity, which has promoted countless studies on the modification of naturally occurring steroids in search of new and more active compounds (2). Among these modifications, hydroxylation is one of the most important reactions in steroid oxyfunctionalization.…”

Transformation of some 3α-substituted steroids by Aspergillus tamarii KITA reveals stereochemical restriction of steroid binding orientation in the minor hydroxylation pathway

“…Interestingly the 3␣-acetate analogue (8) appeared to inhibit the activity of the monooxygenase activity where Baeyer-Villiger oxidation of the C-17 ketone was first observed at 48 h. Overall lower yields of lactones (9, 10) were obtained following transformation of the 3␣-acetate in comparison to the transformation of the 3␣-alcohol (7), a pattern also paralleled with the recombinant technology [24].…”

“…Generation of the lactone (9) was achieved in significant yield (53%) following incubation of the 17-keto-3␣-ol (7) with the Baeyer-Villiger monooxygenase activity observed in the first 24 h. In comparison to a recently reported recombinant cyclohexanone monooxygenase [24] on identical steroidal substrates (7, 8) our whole cell system achieves a 6 times higher yield starting with an identical substrate. Interestingly the 3␣-acetate analogue (8) appeared to inhibit the activity of the monooxygenase activity where Baeyer-Villiger oxidation of the C-17 ketone was first observed at 48 h. Overall lower yields of lactones (9, 10) were obtained following transformation of the 3␣-acetate in comparison to the transformation of the 3␣-alcohol (7), a pattern also paralleled with the recombinant technology [24].…”

Cloning, expression and characterization of a versatile Baeyer-Villiger monooxygenase from Dietzia sp. D5

“…The most studied member of this group of BVMOs is CPDMO, a BVMO from Pseudomonas sp. HI-70 (Iwaki et al [2006]; Beneventi et al [2009]; Fink et al [2011]). The other BVMOs belonging to this group are both of microbial and fungal origin (Miyamoto et al [1995]; Jiang et al [2009]; Qiao et al [2011]) and are known to be very versatile in terms of their substrate scope, and efficiently catalyze the oxidation of a wide range of substrates, which indicates a broader application potential (Fink et al [2012]; Bianchi et al [2013]).…”