University of Groningen Flavoprotein monooxygenases, a diverse class of oxidative biocatalysts Berkel, W.J.H.; Kamerbeek, N.M; Fraaije, M.W. Published in: Journal of Biotechnology DOI: 10.1016/j.jbiotec.2006.03.044 IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below. Document Version Publisher's PDF, also known as Version of record Publication date: 2006 Link to publication in University of Groningen/UMCG research database Citation for published version (APA): Berkel, W. J. H., Kamerbeek, N. M., & Fraaije, M. W. (2006). Flavoprotein monooxygenases, a diverse class of oxidative biocatalysts. 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For technical reasons the number of authors shown on this cover page is limited to 10 maximum. Download date: 03-10-2021 Journal of Biotechnology 124 (2006) 670–689 Review Flavoprotein monooxygenases, a diverse class of oxidative biocatalysts W.J.H. van Berkel a, N.M. Kamerbeek b, M.W. Fraaije c,∗ a Laboratory of Biochemistry, Department of Agrotechnology and Food Sciences, Wageningen University, Dreijenlaan 3, 6703 HA Wageningen, The Netherlands b Department of Blood Cell Research, Sanquin Research, Plesmanlaan 125, 1066 CX Amsterdam, The Netherlands c Laboratory of Biochemistry, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Nijenborgh 4, 9747 AG Groningen, The Netherlands Received 17 October 2005; received in revised form 21 February 2006; accepted 29 March 2006 Abstract During the last decades a large number of flavin-dependent monooxygenases have been isolated and studied. This has revealed that flavoprotein monooxygenases are able to catalyze a remarkable wide variety of oxidative reactions such as regioselective hydroxylations and enantioselective sulfoxidations. These oxidation reactions are often difficult, if not impossible, to be achieved using chemical approaches. Analysis of the available genome sequences has indicated that many more flavoprotein monooxy- genases exist and await biocatalytic exploration. Based on the known biochemical properties of a number of flavoprotein monooxygenases and sequence and structural analyses, flavoprotein monooxygenases can be classified into six distinct flavopro- tein monooxygenase subclasses. This review provides an inventory of known flavoprotein monooxygenases belonging to these different enzyme subclasses. Furthermore, the biocatalytic potential of a selected number of flavoprotein monooxygenases is highlighted. © 2006 Elsevier B.V. All rights reserved. Keywords: Flavoprotein monooxygenase; Hydroxylation; Sulfoxidation; Epoxidation; Baeyer–Villiger oxidation; Biocatalysis Contents 1. Biocatalysis using monooxygenases ...................................................................... 671 2. Flavoprotein monooxygenases ........................................................................... 672 3. Classification of flavoprotein monooxygenases ............................................................ 674 ∗ Corresponding author. Tel.: +31 503634345; fax: +31 503634165. E-mail address: [email protected] (M.W. Fraaije). 0168-1656/$ – see front matter © 2006 Elsevier B.V. All rights reserved. doi:10.1016/j.jbiotec.2006.03.044 W.J.H. van Berkel et al. / Journal of Biotechnology 124 (2006) 670–689 671 3.1. Class A flavoprotein monooxygenases .............................................................. 674 3.1.1. General characteristics of class A flavoprotein monooxygenases .............................. 674 3.1.2. EC members ............................................................................. 677 3.1.3. Other members .......................................................................... 677 3.2. Class B flavoprotein monooxygenases .............................................................. 677 3.2.1. General characteristics of class B flavoprotein monooxygenases............................... 677 3.2.2. EC members ............................................................................. 679 3.2.3. Other members .......................................................................... 679 3.3. Multi-component flavoprotein monooxygenases ..................................................... 679 3.4. Class C flavoprotein monooxygenases .............................................................. 679 3.4.1. General characteristics of class C flavoprotein monooxygenases............................... 679 3.4.2. EC members ............................................................................. 680 3.4.3. Other members .......................................................................... 680 3.5. Class D flavoprotein monooxygenases .............................................................. 680 3.5.1. General characteristics of class D flavoprotein monooxygenases .............................. 680 3.5.2. EC members ............................................................................. 681 3.5.3. Other members .......................................................................... 681 3.6. Class E flavoprotein monooxygenases .............................................................. 681 3.6.1. General characteristics of class E flavoprotein monooxygenases ............................... 681 3.6.2. Known member .......................................................................... 681 3.7. Class F flavoprotein monooxygenases .............................................................. 681 3.7.1. General characteristics of class F flavoprotein monooxygenases ............................... 681 3.7.2. Some known members .................................................................... 682 4. Biocatalysis with flavin-dependent monooxygenases ....................................................... 682 4.1. Styrene monooxygenase: a selective epoxidation catalyst ............................................. 682 4.2. Hydroxybiphenyl 3-monooxygenase: an example of monooxygenase engineering ....................... 683 4.3. Monooxygenases involved in desulfurization ........................................................ 683 4.4. Cyclohexanone monooxygenase: a versatile monooxygenase ......................................... 683 4.5. Phenylacetone monooxygenase: a new and thermostable oxygenating biocatalyst ....................... 684 5. Concluding remarks .................................................................................... 684 References ............................................................................................. 685 1. Biocatalysis using monooxygenases biocatalytic applications involving monooxygenases is the fact that most of these enzymes depend on expen- Efficient and specific insertion of one oxygen atom sive coenzymes for their activities. Recent develop- into an organic substrate is a reaction that is difficult to ments have alleviated some of these practical issues by, perform by chemical means. Although some catalysts e.g. employing improved expression systems, devel- have been developed that are able to catalyze specific oping coenzyme regeneration systems or coenzyme oxygenations, the exquisite specificity of enzymes per- replacements. Also, in recent years several enzymes forming monooxygenations (monooxygenases) is still have been discovered that can perform hydroxylations unequaled. This makes this class of enzymes (EC 1.13 while being coenzyme-independent. As a consequence and EC 1.14) of great interest for synthetic purposes. of these developments, effective practical biocatalytic In the last few decades a multitude of monooxyge- applications with monooxygenases are in reach. nases have been discovered revealing a wide range The efforts in discovery and characterization of of reactivities and selectivities. Nevertheless, only a monooxygenases have revealed that a number of differ- small number have been explored for their synthetic ent types of enzymes have evolved in nature to catalyze value. This is partly due to a limited availability of monooxygenation reactions. One of the best known enzymes, e.g. due to difficulties of enzyme expression examples is the family of cytochrome P450 monooxy- or isolation. Another practical problem associated with genases. These heme-containing enzymes (EC 1.14.13, 672 W.J.H. van Berkel et al. / Journal of Biotechnology 124 (2006) 670–689 EC 1.14.14 and EC 1.14.15) are relatively abundant, flavin-dependent monooxygenases is given with spe- occur in many isoforms, and have been shown to cat- cial emphasis on members that display interesting bio- alyze a plethora of specific oxygenations. P450 genes catalytic properties.