Heme-iron oxygenases: powerful industrial biocatalysts?

Julsing, Mattijs K.; Cornelissen, Sjef; Bühler, Bruno; Schmid, Andreas

doi:10.1016/j.cbpa.2008.01.029

Cited by 160 publications

(126 citation statements)

References 65 publications

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“…However, by recycling the organic styrene phase, the overall conversion was increased up to 20-fold (starting from 0.04% to 0.8%) and 70 mM (8.2 g/L) of (S)-styrene oxide was produced. Product titers (8.2 g/L org ) and productivity (~10 g/ L tube /day) achieved in this work are well comparable with other oxygenase-based biocatalytic processes [18][19][20]. To improve the productivity, the capillary length was shortened to 0.5 m, and the flow rates were kept constant in order to reduce the residence time.…”

Section: Resultssupporting

confidence: 71%

Catalytic Pseudomonas taiwanensis VLB120ΔC Biofilms Thrive in a Continuous Pure Styrene Generated by Multiphasic Segmented Flow in a Capillary Microreactor

Halan¹,

Karande²,

Buehler³

et al. 2016

J Flow Chem

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This study investigated the survival and catalytic potential of a single species Pseudomonas taiwanensis VLB120∆C biofilm for the conversion of styrene to (S)-styrene oxide in a multiphasic capillary microreactor containing the highly toxic substrate styrene as a pure phase. The catalytic biofilm was cultivated under high fluidic stress in a continuous three-phase segmented flow system comprising aqueous medium, air, and styrene. This concept required an adaptation period of 7 days, during which P. taiwanensis VLB120∆C developed a biofilm exhibiting a remarkable cellular integrity with nearly 70% intact cells. In a three-phase segmented flow biofilm microreactor, an average specific styrene epoxidation rate of 10 g/L tube /day was achieved continuously for a period of 20 days without any clogging problems. Overall, this note highlights the robustness of biofilms as a promising biocatalyst format for the conversion/synthesis of toxic organic chemicals and the applicability of multiphasic capillary microreactors for biofilm based catalysis.

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Section: Resultssupporting

confidence: 71%

Catalytic Pseudomonas taiwanensis VLB120ΔC Biofilms Thrive in a Continuous Pure Styrene Generated by Multiphasic Segmented Flow in a Capillary Microreactor

Halan¹,

Karande²,

Buehler³

et al. 2016

J Flow Chem

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“…In recent years, the number of publications about the potential applications of P450 enzymes for the production of drug or drug-related compounds of pharmaceutical interest has continuously grown (Julsing et al, 2008). This progress can directly be of use for efficient and timesaving production of human drug metabolites.…”

Section: Discussionmentioning

confidence: 99%

CYP267A1 and CYP267B1 from Sorangium cellulosum So ce56 are Highly Versatile Drug Metabolizers

Kern

Khatri

Litzenburger

et al. 2016

Drug Metabolism and Disposition

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The guidelines of the Food and Drug Administration and International Conference on Harmonization have highlighted the importance of drug metabolites in clinical trials. As a result, an authentic source for their production is of great interest, both for their potential application as analytical standards and for required toxicological testing. Since we have previously shown promising biotechnological potential of cytochromes P450 from the soil bacterium Sorangium cellulosum So ce56, herein we investigated the CYP267 family and its application for the conversion of commercially available drugs including nonsteroidal anti-inflammatory, antitumor, and antihypotensive drugs. The CYP267 family, especially CYP267B1, revealed the interesting ability to convert a broad range of substrates. We established substrate-dependent extraction protocols and also optimized the reaction conditions for the in vitro experiments and Escherichia coli-based whole-cell bioconversions. We were able to detect activity of CYP267A1 toward seven out of 22 drugs and the ability of CYP267B1 to convert 14 out of 22 drugs. Moderate to high conversions (up to 85% yield) were observed in our established whole-cell system using CYP267B1 and expressing the autologous redox partners, ferredoxin 8 and ferredoxin-NADP + reductase B. With our existing setup, we present a system capable of producing reasonable quantities of the human drug metabolites 49-hydroxydiclofenac, 2-hydroxyibuprofen, and omeprazole sulfone. Due to the great potential of converting a broad range of substrates, wild-type CYP267B1 offers a wide scope for the screening of further substrates, which will draw further attention to future biotechnological usage of CYP267B1 from S. cellulosum So ce56.

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“…Poor stability and low turnover rates, as well as the need for expensive cofactors, are among their greater limitations. To overcome some of these issues, industrial processes, for example, typically use fermentation reactors [20].…”

Section: P450 Biocatalystsmentioning

confidence: 99%

“…Most mammalian P450 enzymes show unequalled substrate promiscuity among P450s [2,20,66,67]. This is an attractive quality for a useful and versatile biocatalyst, and can eliminate the need for protein mutagenesis to expand the substrate scope.…”

Section: Mammalian P450smentioning

confidence: 99%

Use of Chemical Auxiliaries to Control P450 Enzymes for Predictable Oxidations at Unactivated C-H Bonds of Substrates

Auclair

Polic

2015

Advances in Experimental Medicine and Biology

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Cytochrome P450 enzymes (P450s) have the ability to oxidize unactivated C-H bonds of substrates with remarkable regio-and stereoselectivity. Comparable selectivity for chemical oxidizing agents is typically difficult to achieve. Hence, there is an interest in exploiting P450s as potential biocatalysts. Despite their impressive attributes, the current use of P450s as biocatalysts is limited. While bacterial P450 enzymes typically show higher activity, they tend to be highly selective for one or a few substrates. On the other hand, mammalian P450s, especially the drugmetabolizing enzymes, display astonishing substrate promiscuity. However, product prediction continues to be challenging. This review discusses the use of small molecules for controlling P450 substrate specificity and product selectivity. The focus will be on two approaches in the area: (1) the use of decoy molecules, and (2) the application of substrate engineering to control oxidation by the enzyme.

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Heme-iron oxygenases: powerful industrial biocatalysts?

Cited by 160 publications

References 65 publications

Catalytic Pseudomonas taiwanensis VLB120ΔC Biofilms Thrive in a Continuous Pure Styrene Generated by Multiphasic Segmented Flow in a Capillary Microreactor

Catalytic Pseudomonas taiwanensis VLB120ΔC Biofilms Thrive in a Continuous Pure Styrene Generated by Multiphasic Segmented Flow in a Capillary Microreactor

CYP267A1 and CYP267B1 from Sorangium cellulosum So ce56 are Highly Versatile Drug Metabolizers

Use of Chemical Auxiliaries to Control P450 Enzymes for Predictable Oxidations at Unactivated C-H Bonds of Substrates

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