HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 281, Issue 1, 27-35, January 6, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: 281/1/27    most recent M506146200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Valton, J. Articles by Nivière, V. Search for Related Content PubMed PubMed Citation Articles by Valton, J. Articles by Nivière, V. Social Bookmarking                      What's this?

An Aromatic Hydroxylation Reaction Catalyzed by a Two-component FMN-dependent Monooxygenase

THE ActVA-ActVB SYSTEM FROM STREPTOMYCES COELICOLOR^*

Julien Valton, Marc Fontecave1, Thierry Douki, Steven G. Kendrew¶, and Vincent Nivière2

From the Laboratoire de Chimie et Biochimie des Centres Redox Biologiques, DRDC-CEA/CNRS/Université Joseph Fourier, 17 Avenue des Martyrs, 38054 Grenoble Cedex 9, France, the Laboratoire des Lésions des Acides Nucléiques, DRFMC-SCIB, UMR-E3 CEA-UJF, CEA-Grenoble, 17 Avenue des Martyrs, 38054 Grenoble Cedex 9, France, and the ^¶Biotica Technology Ltd., Essex CB10 1XL, United Kingdom

The ActVA-ActVB system from Streptomyces coelicolor isatwo-component flavin-dependent monooxygenase that belongs to an emerging class of enzymes involved in various oxidation reactions in microorganisms. The ActVB component is a NADH:flavin oxidoreductase that provides a reduced FMN to the second component, ActVA the proper monooxygenase. In this work, we demonstrate that the ActVA-ActVB system catalyzes the aromatic monohydroxylation of dihydrokalafungin by molecular oxygen. In the presence of reduced FMN and molecular oxygen, the ActVA active site accommodates and stabilizes an electrophilic flavin FMN-OOH hydroperoxide intermediate species as the oxidant. Surprisingly, we demonstrate that the quinone form of dihydrokalafungin is not oxidized by the ActVA-ActVB system, whereas the corresponding hydroquinone is an excellent substrate. The enantiomer of dihydrokalafungin, nanaomycin A, as well as the enantiomer of kalafungin, nanaomycin D, are also substrates in their hydroquinone forms. The previously postulated product of the ActVA-ActVB system, the antibiotic actinorhodin, was not found to be formed during the oxidation reaction.

Received for publication, June 6, 2005 , and in revised form, September 30, 2005.

^* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence may be addressed. Tel.: 33-4-38-78-91-03; Fax: 33-4-38-78-91-24; E-mail: mfontecave{at}cea.fr. ² To whom correspondence may be addressed. Tel.: 33-4-38-78-91-09; Fax: 33-4-38-78-91-24; E-mail: vniviere{at}cea.fr.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				J. Valton, C. Mathevon, M. Fontecave, V. Niviere, and D. P. Ballou Mechanism and Regulation of the Two-component FMN-dependent Monooxygenase ActVA-ActVB from Streptomyces coelicolor J. Biol. Chem., April 18, 2008; 283(16): 10287 - 10296. [Abstract] [Full Text] [PDF]

				S.-H. Kim, T. Hisano, K. Takeda, W. Iwasaki, A. Ebihara, and K. Miki Crystal Structure of the Oxygenase Component (HpaB) of the 4-Hydroxyphenylacetate 3-Monooxygenase from Thermus thermophilus HB8 J. Biol. Chem., November 9, 2007; 282(45): 33107 - 33117. [Abstract] [Full Text] [PDF]

				J. Sucharitakul, P. Chaiyen, B. Entsch, and D. P. Ballou Kinetic Mechanisms of the Oxygenase from a Two-component Enzyme, p-Hydroxyphenylacetate 3-Hydroxylase from Acinetobacter baumannii J. Biol. Chem., June 23, 2006; 281(25): 17044 - 17053. [Abstract] [Full Text] [PDF]