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In: Vitamin B: New Research ISBN 978-1-60021-782-1

Editor: Charlyn M. Elliot, pp. 81-98 © 2008 Nova Science Publishers, Inc.

Chapter V

NEW BACTERIAL COBALAMIN-DEPENDENT

COA-CARBONYL MUTASES INVOLVED IN

DEGRADATION PATHWAYS

Thore Rohwerder1,∗ and Roland H. Müller2

1

Aquatic Biotechnology, Biofilm Centre, University Duisburg-Essen, Geibelstr. 41, D47057 Duisburg, Germany;

2

Department of Environmental Microbiology, Helmholtz Centre for Environmental

Research UFZ, Permoserstr. 15, D-04318 Leipzig, Germany.

ABSTRACT

The adenosylcobalamin-dependent CoA-carbonyl mutases catalyze the 1,2-

rearrangement of carbonyl groups reversibly converting branched-chain carbonic acids

into straight-chain ones. Currently, this enzyme group comprises of only two known

mutases, the extensively studied methylmalonyl-CoA mutase (MCM, EC 5.4.99.2) and

isobutyryl-CoA mutase (ICM, EC 5.4.99.13). Whereas MCM is widespread among

bacteria and animals ICM seems to be restricted to bacteria and has thus far only been

characterized in Streptomyces spp. Both enzymes have a rather limited substrate

spectrum and function effectively merely with their natural substrates methylmalonylCoA and isobutyryl-CoA, respectively. Interestingly, we have recently discovered a

novel bacterial CoA-carbonyl mutase catalyzing the conversion of 2-hydroxyisobutyrylCoA into 3-hydroxybutyryl-CoA (Rohwerder et al. 2006, Appl. Environ. Microbiol.

72:4128). This enzyme plays a central role in the productive degradation of compounds

containing a tert-butyl group such as the common fuel additives methyl and ethyl tertbutyl ether. Similar enzymes are proposed to be involved in the conversion of pivalic

acid and in the degradation of alkanes and alkylated aromatic hydrocarbons via anaerobic

pathways employing addition to fumarate. Since all these compounds are important

∗

 Correspondence concerning this article should be addressed to: Thore Rohwerder, Aquatic Biotechnology,

Biofilm Centre, University Duisburg-Essen, Geibelstr. 41, D-47057 Duisburg, Germany, e-mail:

thore.rohwerder@uni-due.de.

82 Thore Rohwerder and Roland H. Müller

pollutants of water and soil, cobalamin and the new CoA-carbonyl mutases play a thus

far not realized role in natural as well as induced bioremediation processes. Therefore,

we summarize in this chapter the known reactions and also speculate about further

pathways which have not yet been associated with CoA-carbonyl mutase activity. In

addition, the enzyme structure and the herewith possibly associated evolution of substrate

specificity are outlined. Finally, energetic and kinetic consequences are discussed which

may result from employing a cobalamin-dependent enzyme for dissimilatory pathways.

INTRODUCTION

The cobalamin-dependent CoA-carbonyl mutases are a group of enzymes catalyzing the

spectacular 1,2-rearrangement of the CoA thioester moiety of CoA-activated carbonic acids.

In this reaction, the cofactor adenosylcobalamin is used to create radical intermediates.

Currently, only two representatives of this enzyme group are known, the extensively studied

and widespread methylmalonyl-CoA mutase (MCM, EC 5.4.99.2) and isobutyryl-CoA

mutase (ICM, EC 5.4.99.13). MCM catalyzes the reversible and stereospecific conversion of

(R)-methylmalonyl-CoA into succinyl-CoA (eq. 1).

H

-

OOC COSCoA

CH3

H

-

OOC

COSCoA

H2C

H

MCM

(R)-methylmalonyl-CoA succinyl-CoA

(1)

This mutase has been found in a variety of bacteria and also in animals, in which the

enzyme is located in the mitochondria (Gruber & Kratky 2001). The animal MCM is

involved in the conversion of branched-chain amino acids, odd-chain fatty acids and

cholesterol via propionate and methylmalonyl-CoA into succinyl-CoA (Willard & Rosenberg

1980). Any impairment of the mutase results in a serious disorder of organic acid metabolism

termed methylmalonic aciduria (Deodato et al. 2006). In contrast, bacterial propionate

degradation is much more diverse and, consequently, MCM catalysis is not always required

(Textor et al. 1997). However, additional functions of bacterial MCMs are known, including

also the catalysis of the reverse reaction from succinyl-CoA to methylmalonyl-CoA. For

example, in some fermenting bacteria, such as Propionibacterium shermanii, propionate is

not a metabolic intermediate but the end product of the anaerobic degradation of lactate or

pyruvate. Here, MCM is employed for synthesizing propionate from tricarboxylic acid-cycle

(TCC) intermediates via methylmalonyl-CoA (Allen et al. 1964). In Streptomyces spp., MCM

together with ICM is involved in secondary metabolism, providing building blocks for

polyketide antibiotic synthesis (Birch et al. 1993).

In contrast to MCM, ICM seems to be restricted to bacteria and has thus far only been

characterized in the above mentioned Streptomyces spp. (Ratnatilleke et al. 1999; Zerbe-

New Bacterial CoA-Carbonyl Mutases 83

Burkhardt et al. 1998). It catalyzes the reversible conversion of isobutyryl-CoA into butyrylCoA. Although stereospecificity is not as stringent as in MCM, an analogous retention of

configuration is also predominating in ICM (Moore et al. 1995) (eq. 2).

(2)