Oxidation of Steroids by Micro Örganisms. Iii. Side Chain Degradation, Ring D-Cleavage and Dehydrogenation in Ring A

Fried, Josef; Thoma, R. W.; Klingsberg, Anna

doi:10.1021/ja01118a530

Cited by 172 publications

(44 citation statements)

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“…11 The isolation of testolactone (7) and other D-ring oxidized steroids from the fermentation with progesterone (8), testosterone (9), and cortexolone (10) by penicillia and aspergilli species were reported by three independent research groups in 1953. 12,78 Although the enzymes were never identified by the authors, they speculated that the biooxidation follows the same principle as the chemical oxidation using peracids, based on the fact that they could isolate considerable quantities of partially oxidized intermediates. 12 Large scale experiments with up to 30 L fungal cultures were conducted and confirmed that the metabolic degradation of steroids by fungal strains proceeds as follows: progesterone (8) to progesterone acetate (11) to testosterone (9) to androst-4-ene-3,7-dione (12), and finally to testolactone (7) ( Figure 6).…”

Section: Baeyeràvilliger Monooxygenases In Steroidmentioning

confidence: 99%

“…12,78 Although the enzymes were never identified by the authors, they speculated that the biooxidation follows the same principle as the chemical oxidation using peracids, based on the fact that they could isolate considerable quantities of partially oxidized intermediates. 12 Large scale experiments with up to 30 L fungal cultures were conducted and confirmed that the metabolic degradation of steroids by fungal strains proceeds as follows: progesterone (8) to progesterone acetate (11) to testosterone (9) to androst-4-ene-3,7-dione (12), and finally to testolactone (7) ( Figure 6). 79 Experiments by Rakhit and Singh with 17R-deuteroprogesterone as starting material and extensive studies by Carlstr€ om confirmed the previously assumed pathway and mechanism of the microbial degradation of the side chain of steroids and D-ring lactonization.…”

Section: Baeyeràvilliger Monooxygenases In Steroidmentioning

confidence: 99%

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Baeyer−Villiger Monooxygenases: More Than Just Green Chemistry

2011

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Section: Baeyeràvilliger Monooxygenases In Steroidmentioning

confidence: 99%

Section: Baeyeràvilliger Monooxygenases In Steroidmentioning

confidence: 99%

Baeyer−Villiger Monooxygenases: More Than Just Green Chemistry

2011

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“…(37). This type of microbial reaction was reported as early as 1953 with the removal of the C-17 side chain of progesterone (22), but only in 1969 was it proposed by Forney and Markovetz (19) that the degradation of 2-tridecanone by some Pseudomonas species involves a oxygenase which converts the 2-tridecanone into an ester analogous to a Baeyer-Villiger reaction and that the ester is hydrolyzed to acetate and a primary alcohol. Both oxygenase and esterase activities were found in crude extracts of the Pseudomonas spp.…”

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confidence: 99%

Degradation of Alkyl Methyl Ketones by Pseudomonas veronii MEK700

et al. 2007

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Pseudomonas veronii MEK700 was isolated from a biotrickling filter cleaning 2-butanone-loaded waste air. The strain is able to grow on 2-butanone and 2-hexanol. The genes for degradation of short chain alkyl methyl ketones were identified by transposon mutagenesis using a newly designed transposon, mini-Tn5495, and cloned in Escherichia coli. DNA sequence analysis of a 15-kb fragment revealed three genes involved in methyl ketone degradation. The deduced amino acid sequence of the first gene, mekA, had high similarity to BaeyerVilliger monooxygenases; the protein of the second gene, mekB, had similarity to homoserine acetyltransferases; the third gene, mekR, encoded a putative transcriptional activator of the AraC/XylS family. The three genes were located between two gene groups: one comprising a putative phosphoenolpyruvate synthase and glycogen synthase, and the other eight genes for the subunits of an ATPase. Inactivation of mekA and mekB by insertion of the mini-transposon abolished growth of P. veronii MEK700 on 2-butanone and 2-hexanol. The involvement of mekR in methyl ketone degradation was observed by heterologous expression of mekA and mekB in Pseudomonas putida. A fragment containing mekA and mekB on a plasmid was not sufficient to allow P. putida KT2440 to grow on 2-butanone. Not until all three genes were assembled in the recombinant P. putida was it able to use 2-butanone as carbon source. The Baeyer-Villiger monooxygenase activity of MekA was clearly demonstrated by incubating a mekB transposon insertion mutant of P. veronii with 2-butanone. Hereby, ethyl acetate was accumulated. To our knowledge, this is the first time that ethyl acetate by gas chromatographic analysis has been definitely demonstrated to be an intermediate of MEK degradation. The mekB-encoded protein was heterologously expressed in E. coli and purified by immobilized metal affinity chromatography. The protein exhibited high esterase activity towards short chain esters like ethyl acetate and 4-nitrophenyl acetate.

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“…The formation of a double bond in the 1,2 position of the A ring of steroids by microbiological methods was first reported by Vischer & Wettstein (1953) and Fried et al (1953). The microbiological dehydrogenation of 17,21-dihydroxypregn-4-ene-3,20-dione (I) (Reichstein's compound S) to 17,21-dihydroxypregna-1,4-diene-3,20-dione (II) (Scheme 1) by fungi of the genus Fusarium (Fusarium solani) and species of the genera Calonectria, Ophiobolus and Alternaria was reported by Vischer et al (1955a).…”

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confidence: 93%