Cunninghamella – A microbial model for drug metabolism studies – A review

Asha, S.; Vidyavathi, M.

doi:10.1016/j.biotechadv.2008.07.005

Cited by 207 publications

(161 citation statements)

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“…To our knowledge, the P. putida CBB5 methylxanthine Ndm provides the first concrete example of a Rieske non-haem iron oxygenase with broadbased N-demethylase activity on a number of purine alkaloids. N-Demethylation (or N-dealkylation) reactions in eukaryotes and prokaryotes are known to be catalysed only by cytochrome P450s (Abel et al, 2003;Asha & Vidyavathi, 2009;Caubet et al, 2004;Cha et al, 2001;Guengerich, 2001;Tassaneeyakul et al, 1994), various flavo-enzymes (Chang et al, 2007;Kvalnes-Krick & Jorns, 1986;Meskys et al, 2001;Nishiya & Imanaka, 1993;Phillips et al, 1998;Shi et al, 2004;Wagner, 1982) and a ketoglutarate-dependent non-haem iron oxygenase (Tsukada et al, 2006). This study therefore broadens our understanding of the possible enzymic mechanism for N-demethylation and will aid the discovery of new microbial N-demethylases in the future.…”

Section: Discussionmentioning

confidence: 76%

Characterization of a broad-specificity non-haem iron N-demethylase from Pseudomonas putida CBB5 capable of utilizing several purine alkaloids as sole carbon and nitrogen source

Summers

Louie

et al. 2011

Microbiology

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N-Demethylation of many xenobiotics and naturally occurring purine alkaloids such as caffeine and theobromine is primarily catalysed in higher organisms, ranging from fungi to mammals, by the well-studied membrane-associated cytochrome P450s. In contrast, there is no well-characterized enzyme for N-demethylation of purine alkaloids from bacteria, despite several reports on their utilization as sole source of carbon and nitrogen. Here, we provide what we believe to be the first detailed characterization of a purified N-demethylase from Pseudomonas putida CBB5. The soluble N-demethylase holoenzyme is composed of two components, a reductase component with cytochrome c reductase activity (Ccr) and a two-subunit N-demethylase component (Ndm). Ndm, with a native molecular mass of 240 kDa, is composed of NdmA (40 kDa) and NdmB (35 kDa). Ccr transfers reducing equivalents from NAD(P)H to Ndm, which catalyses an oxygen-dependent N-demethylation of methylxanthines to xanthine, formaldehyde and water. Paraxanthine and 7-methylxanthine were determined to be the best substrates, with apparent K m and kcat values of 50.4±6.8 μM and 16.2±0.6 min−1, and 63.8±7.5 μM and 94.8±3.0 min−1, respectively. Ndm also displayed activity towards caffeine, theobromine, theophylline and 3-methylxanthine, all of which are growth substrates for this organism. Ndm was deduced to be a Rieske [2Fe–2S]-domain-containing non-haem iron oxygenase based on (i) its distinct absorption spectrum and (ii) significant identity of the N-terminal sequences of NdmA and NdmB with the gene product of an uncharacterized caffeine demethylase in P. putida IF-3 and a hypothetical protein in Janthinobacterium sp. Marseille, both predicted to be Rieske non-haem iron oxygenases.

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Section: Discussionmentioning

confidence: 76%

Characterization of a broad-specificity non-haem iron N-demethylase from Pseudomonas putida CBB5 capable of utilizing several purine alkaloids as sole carbon and nitrogen source

Summers

Louie

et al. 2011

Microbiology

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“…The ability of Cunninghamella sp. to biotransform a wide range of xenobiotics and drugs using both phase I and phase II mechanisms is well-known due to the similarity to the mammalian metabolism (Asha and Vidyavathi 2009;Murphy 2015). Therefore, a search for other TBT by-products was performed.…”

Section: Discussionmentioning

confidence: 99%

Tributyltin (TBT) biodegradation induces oxidative stress of Cunninghamella echinulata

Soboń

Szewczyk

Długoński

2016

International Biodeterioration & Biodegradation

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HighlightsEfficient TBT biodegradation to DBT, MBT and tin-hydroxylated byproduct was observed. TBT changed the protein and free amino acid profile. Markers of oxidative stress were upregulated in the presence of TBT. AbstractTributyltin (TBT) is one of the most deleterious compounds introduced into natural environment by humans. The ability of Cunninghamella echinulata to degrade tributyltin (TBT) (5 mg l -1 ) as well as the effect of the xenobiotic on fungal amino acids composition and proteins profile were examined. C. echinulata removed 91% of the initial biocide concentration and formed less hazardous compounds dibutyltin (DBT) and monobutyltin (MBT). Moreover, the fungus produced a hydroxylated metabolite (TBTOH), in which the hydroxyl group was bound directly to the tin atom. Proteomics analysis showed that in the presence of TBT, the abundances of 22 protein bands were changed and the unique overexpressions of peroxiredoxin and nuclease enzymes were observed. Determination of free amino acids showed significant changes in the amounts of 19 from 23 detected metabolites. A parallel increase in the level of selected amino acids such as betaine, alanine, aminoisobutyrate or proline and peroxiredoxin enzyme in TBT-containing cultures revealed that TBT induced oxidative stress in the examined fungus.

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“…1,2 This mechanism has been developed by microbes to acclimatize to environmental changes and it is useful in a wide range of biotechnological processes. 3 The most significant aspect of biotransformation is that it maintains the original carbon skeleton after obtaining the products.…”

Section: Introductionmentioning

confidence: 99%

Microbial Biotransformation: A Process for Chemical Alterations

Sreedharan¹,

Singh²,

Singh³

2017

JBMOA

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Biotransformation is a process by which organic compounds are transformed from one form to another to reduce the persistence and toxicity of the chemical compounds. This process is aided by major range of microorganisms and their products such as bacteria, fungi and enzymes. Biotransformations can also be used to synthesize compounds or materials, if synthetic approaches are challenging. Natural transformation process is slow, nonspecific and less productive. Microbial biotransformations or microbial biotechnology are gaining importance and extensively utilized to generate metabolites in bulk amounts with more specificity. This review was conceived to assess the impact of microbial biotransformation of steroids, antibiotics, various pollutants and xenobiotic compounds.

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Cunninghamella – A microbial model for drug metabolism studies – A review

Cited by 207 publications

References 146 publications

Characterization of a broad-specificity non-haem iron N-demethylase from Pseudomonas putida CBB5 capable of utilizing several purine alkaloids as sole carbon and nitrogen source

Characterization of a broad-specificity non-haem iron N-demethylase from Pseudomonas putida CBB5 capable of utilizing several purine alkaloids as sole carbon and nitrogen source

Tributyltin (TBT) biodegradation induces oxidative stress of Cunninghamella echinulata

Microbial Biotransformation: A Process for Chemical Alterations

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