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Annu Rev Microbiol. 1992;46:565-601.

Functional and evolutionary relationships among diverse oxygenases.

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1
Department of Medical Biochemistry, University of Geneva, Switzerland.

Abstract

Oxygenases that incorporate one or two atoms of dioxygen into substrates are found in many metabolic pathways. In this article, representative oxygenases, principally those found in bacterial pathways for the degradation of hydrocarbons, are reviewed. Monooxygenases, discussed in this chapter, incorporate one hydroxyl group into substrates. In this reaction, two atoms of dioxygen are reduced to one hydroxyl group and one H2O molecule by the concomitant oxidation of NAD(P)H. Dioxygenases catalyze the incorporation of two atoms of dioxygen into substrates. Two types of dioxygenases, aromatic-ring dioxygenases and aromatic-ring-cleavage dioxygenases, are discussed. The aromatic-ring dioxygenases incorporate two hydroxyl groups into aromatic substrates, and cis-diols are formed. This reaction also requires NAD(P)H as an electron donor. Aromatic-ring-cleavage dioxygenases incorporate two atoms of dioxygen into aromatic substrates, and the aromatic ring is cleaved. This reaction does not require an external reductant. All the oxygenases possess a cofactor, a transition metal, flavin or pteridine, that interacts with dioxygen. The concerted reactions between dioxygen and carbon in organic compounds are spin forbidden. The cofactor is used to overcome this restriction. For the oxygenases that require the NAD(P)H cofactor, the enzyme reaction is separated into two steps, the oxidation of NAD(P)H to generate two reducing equivalents, and the hydroxylation of substrates. Flavoprotein hydroxylases that catalyze the monohydroxylation of the aromatic ring carry out these two reactions on a single polypeptide chain. In other oxygenases, the NAD(P)H oxidation and a hydroxylation reaction are catalyzed by two separate polypeptides that are linked by a short electron-transport chain. Two reducing equivalents generated by the oxidation of NAD(P)H are transferred through the electron-transport chain to the cofactor on a hydroxylase component that they reduce. Dioxygen couples with the reduced cofactor and subsequently hydroxylates substrates. The electron-transport chains associated with oxygenases contain at least two redox centers. The first redox center is usually a flavin, while the second is an iron-sulfur cluster. The electron transport is initiated by a single two-electron transfer from NAD(P)H to a flavin, followed by two single-electron transfers from the flavin to an iron-sulfur cluster. The primary sequences of many oxygenases have been determined, and according to their sequence similarities, the oxygenases can be grouped into several protein families. Among proteins of the same family, the sequences in regions involved in cofactor binding are strongly conserved. Local sequence similarities are also observed among oxygenases from different families, primarily in regions involved in cofactor binding.

[Indexed for MEDLINE]

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