Microbial transformation of androstenedione by <i>Cladosporium sphaerospermum</i> and <i>Ulocladium chartarum</i>

Yildirim, Kudret; Kuru, Ali; Küçükbaşol, Eda

doi:10.1080/10242422.2019.1604690

Cited by 11 publications

(5 citation statements)

References 28 publications

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“…In addition, for the first time, we found compounds 6β–OH–AD ( l ) and 6β–OH–TS ( m ) for this strain, which indicates the presence of a previously undiscovered 6β-hydroxylating activity in this strain. Together with the current study, 23 possible steroid products have been described in the literature after steroid transformation of AD by fungal strains from the Cladosporiaceae and Pleosporaceae families [ 20 , 22 , 23 , 32 , 41 ] ( Table 2 , Figure 5 ). If we take into account the control strain C. lunata RNCIM F-981, then 30.4% (7 out of 23) of the steroid products found in our study were previously described ( e , k , l , m , o , p , and q ) and 26% (6 out of 23) of steroidal products are described for the first time ( a , b , f , g , i , and r ) ( Figure 5 ).…”

Section: Resultsmentioning

confidence: 52%

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Biotransformation of Androstenedione by Filamentous Fungi Isolated from Cultural Heritage Sites in the State Tretyakov Gallery

Zhgun

Потапов

Avdanina

et al. 2022

Biology

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The transformation of steroids by microorganisms is widely used in medical biotechnology. A huge group of filamentous fungi is one of the most promising taxa for screening new biocatalytic reactions in order to obtain pharmaceutically significant steroids. In this work, we screened 10 filamentous fungi-destructors of egg tempera for the ability to biotransform androst-4-en-3,17-dione (AD) during cultivation in a liquid nutrient medium or in a buffer solution. These taxonomically unrelated strains, belonging to the classes Eurotiomycetes, Dothideomycetes and Sordariomycetes, are dominant representatives of the microbiome from halls where works of tempera painting are stored in the State Tretyakov Gallery (STG, Moscow, Russia). Since the binder of tempera paints, egg yolk, contains about 2% cholesterol, these degrading fungi appear to be a promising group for screening for steroid converting activity. It turned out that all the studied fungi-destructors are able to transform AD. Some strains showed transformation efficiency close to the industrial strain Curvularia lunata RNCIM F-981. In total, 33 steroids formed during the transformation of AD were characterized, for 19 of them the structure was established by gas chromatography/mass spectrometry analysis. In this work, we have shown for the first time that fungi-destructors of tempera paintings can efficiently transform steroids.

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Section: Resultsmentioning

confidence: 52%

“…However, for the overwhelming majority of molds, the “capacity” of steroid biotransformation has not been characterized [ 2 , 19 ]. In this regard, among various groups of filamentous fungi, active screening for the ability to transform pharmaceutically significant steroids is being carried out [ 20 , 21 , 22 , 23 ].…”

Section: Introductionmentioning

confidence: 99%

Biotransformation of Androstenedione by Filamentous Fungi Isolated from Cultural Heritage Sites in the State Tretyakov Gallery

Zhgun

Потапов

Avdanina

et al. 2022

Biology

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“…For the hydroxylation of steroids, biotransformation has been widely accepted as an available way due to the comparatively higher stereo-selectivity [ 12 , 13 ], and some microbial hydroxylation methods, such as 11α - and 11β -hydorxylation, have already been industrially applied for decades [ 14 , 15 ]. Up to now, some filamentous fungi that can hydroxylate steroids at C7β have been screened to allow the production of 7β-OHSt by microbial transformations [ 16 – 18 ]. However, these strains have not been applied in the industry because of the insufficient regio- and stereo-selectivities and low conversion rates.…”

Section: Introductionmentioning

confidence: 99%

One-pot biosynthesis of 7β-hydroxyandrost-4-ene-3,17-dione from phytosterols by cofactor regeneration system in engineered mycolicibacterium neoaurum

Zhao

Liu

et al. 2022

Microb Cell Fact

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Background 7β-hydroxylated steroids (7β-OHSt) possess significant activities in anti-inflammatory and neuroprotection, and some of them have been widely used in clinics. However, the production of 7β-OHSt is still a challenge due to the lack of cheap 7β-hydroxy precursor and the difficulty in regio- and stereo-selectively hydroxylation at the inert C7 site of steroids in industry. The conversion of phytosterols by Mycolicibacterium species to the commercial precursor, androst-4-ene-3,17-dione (AD), is one of the basic ways to produce different steroids. This study presents a way to produce a basic 7β-hydroxy precursor, 7β-hydroxyandrost-4-ene-3,17-dione (7β-OH-AD) in Mycolicibacterium, for 7β-OHSt synthesis. Results A mutant of P450-BM3, mP450-BM3, was mutated and engineered into an AD producing strain for the efficient production of 7β-OH-AD. The enzyme activity of mP450-BM3 was then increased by 1.38 times through protein engineering and the yield of 7β-OH-AD was increased from 34.24 mg L− 1 to 66.25 mg L− 1. To further enhance the performance of 7β-OH-AD producing strain, the regeneration of nicotinamide adenine dinucleotide phosphate (NADPH) for the activity of mP450-BM3-0 was optimized by introducing an NAD kinase (NADK) and a glucose-6-phosphate dehydrogenase (G6PDH). Finally, the engineered strain could produce 164.52 mg L− 1 7β-OH-AD in the cofactor recycling and regeneration system. Conclusions This was the first report on the one-pot biosynthesis of 7β-OH-AD from the conversion of cheap phytosterols by an engineered microorganism, and the yield was significantly increased through the mutation of mP450-BM3 combined with overexpression of NADK and G6PDH. The present strategy may be developed as a basic industrial pathway for the commercial production of high value products from cheap raw materials.

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“…Generally, supplementary methods can be used to obtain a sufficient sample amount of metabolites, including chemical methods [11] and small experimental animal models [15], microsomal preparations [16,17], enzyme-catalyzed reactions [18,19], microbial transformation [11,20] and so on. Compared with other methods, microbial transformation is more convenient and economical, especially with the advantages of in vitro large-scale preparation [20][21][22][23][24]. In particular, the filamentous zygote fungus C. elegans has been shown to possess a human-like cytochrome P450 monooxygenase system, including the CYP509A1 isoenzyme that is similar to the CYP51 family, thus producing similar metabolic profiles to mammalian animals [25,26].Sufficient samples for structural characterization based on NMR techniques as well as the evaluation of bioactivity and toxicity can thus be acquired.…”

Section: Introductionmentioning

confidence: 99%

Comprehensive Metabolic Profiling of Euphorbiasteroid in Rats by Integrating UPLC-Q/TOF-MS and NMR as Well as Microbial Biotransformation

Xiao¹,

Wei

Xin

et al. 2022

Metabolites

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Euphorbiasteroid, a lathyrane-type diterpene from Euphorbiae semen (the seeds of Euphorbia lathyris L.), has been shown to have a variety of pharmacological effects such as anti-tumor and anti-obesity. This study aims to investigate the metabolic profiles of euphorbiasteroid in rats and rat liver microsomes (RLMs) and Cunninghamella elegans bio-110930 by integrating ultra-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry (UPLC-Q/TOF-MS), UNIFI software, and NMR techniques. A total of 31 metabolites were identified in rats. Twelve metabolites (M1–M5, M8, M12–M13, M16, M24–M25, and M29) were matched to the metabolites obtained by RLMs incubation and the microbial transformation of C. elegans bio-110930 and their structures were exactly determined through analysis of NMR spectroscopic data. In addition, the metabolic pathways of euphorbiasteroid were then clarified, mainly including hydroxylation, hydrolysis, oxygenation, sulfonation, and glycosylation. Finally, three metabolites, M3 (20-hydroxyl euphorbiasteroid), M24 (epoxylathyrol) and M25 (15-deacetyl euphorbiasteroid), showed significant cytotoxicity against four human cell lines with IC50 values from 3.60 μM to 40.74 μM. This is the first systematic investigation into the in vivo metabolic pathways of euphorbiasteroid and the cytotoxicity of its metabolites, which will be beneficial for better predicting the metabolism profile of euphorbiasteroid in humans and understanding its possible toxic material basis.

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Microbial transformation of androstenedione by Cladosporium sphaerospermum and Ulocladium chartarum

Cited by 11 publications

References 28 publications

Biotransformation of Androstenedione by Filamentous Fungi Isolated from Cultural Heritage Sites in the State Tretyakov Gallery

Biotransformation of Androstenedione by Filamentous Fungi Isolated from Cultural Heritage Sites in the State Tretyakov Gallery

One-pot biosynthesis of 7β-hydroxyandrost-4-ene-3,17-dione from phytosterols by cofactor regeneration system in engineered mycolicibacterium neoaurum

Comprehensive Metabolic Profiling of Euphorbiasteroid in Rats by Integrating UPLC-Q/TOF-MS and NMR as Well as Microbial Biotransformation

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