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Biomedical subjects

G Fuchs

Publications and source records attributed to G Fuchs.

At least 55 records · Page 3Linked to original sources
PubMed1998

Biosynthesis of the diterpene verrucosan-2beta-ol in the phototrophic eubacterium Chloroflexus aurantiacus. A retrobiosynthetic NMR study.

The biosynthesis of verrucosan-2beta-ol in the green phototrophic eubacterium Chloroflexus aurantiacus was investigated by in vivo incorporation of singly or doubly 13C-labeled acetate. The 13C labeling of the isolated diterpene was analyzed by one- and two-dimensional NMR spectroscopy. The 13C-labeling patterns of verrucosan-2beta-ol were compared with the labeling patterns of intermediary metabolites (acetyl-CoA, pyruvate, and glyceraldehyde 3-phosphate) which were deduced from amino acids and nucleosides by retrobiosynthetic analysis. The results show that verrucosan-2beta-ol is synthesized via mevalonate and not via the deoxyxylulose pathway, which was discovered recently in some eubacteria, algae, and plants. A scheme for the formation of the unusual tetracyclic ring system is offered. The cyclization process is initiated by the solvolysis of pyrophosphate from geranyllinaloyl pyrophosphate and the mechanism involves a Wagner-Meerwein rearrangement, a 1,5-hydride shift, and a cyclopropylcarbinyl to cyclopropylcarbinyl rearrangement.

Acetyl Coenzyme A↗
PubMed1998

Single dose vitamin A treatment in acute shigellosis in Bangladesh children: randomised double blind controlled trial.

OBJECTIVE: To evaluate the efficacy of a single large oral dose of vitamin A in treating acute shigellosis in children in Bangladesh. DESIGN: Randomised double blind controlled clinical trial. SETTING: Dhaka Hospital, International Centre for Diarrhoeal Disease Research, Bangladesh. SUBJECTS: 83 children aged 1-7 years with bacteriologically proved shigellosis but no clinical signs of vitamin A deficiency; 42 were randomised to treatment with vitamin A and 41 formed a control group. INTERVENTION: Children were given a single oral dose of 200,000 IU of vitamin A plus 25 IU vitamin E or a control preparation of 25 IU vitamin E. MAIN OUTCOME MEASURES: Clinical cure on study day 5 and bacteriological cure. RESULTS: Baseline characteristics of the subjects in the two treatment groups were similar. Significantly more children in the vitamin A group than in the control group achieved clinical cure (19/42 (45%) v 8/14 (20%); chi 2 = 5.14, 1 df, P = 0.02; risk ratio = 0.68 (95% confidence interval; 0.50 to 0.93)). When cure was determined bacteriologically, the groups had similar rates (16/42 (38%) v 16/41 (39%); chi 2 = 0.02, 1 df, P = 0.89; risk ratio = 0.98 (0.70 to 1.39)). CONCLUSIONS: Vitamin A reduces the severity of acute shigellosis in children living in areas where vitamin A deficiency is a major public health problem.

Acute Disease↗
PubMed1998

Phenylglyoxylate:NAD+ oxidoreductase (CoA benzoylating), a new enzyme of anaerobic phenylalanine metabolism in the denitrifying bacterium Azoarcus evansii.

Phenylglyoxylate (benzoylformate) is an intermediate in the anoxic metabolism of phenylalanine and phenylacetate. It is formed by alpha-oxidation of phenylacetyl-CoA. Phenylglyoxylate is oxidatively decarboxylated by phenylglyoxylate-oxidoreductase to benzoyl-CoA, a central intermediate of anaerobic aromatic metabolism. The phenylglyoxylate oxidizing enzyme activity in the denitrifying bacterium Azoarcus evansii was induced during anaerobic growth with phenylalanine, phenylacetate and phenylglyoxylate, but not with benzoate. The new enzyme phenylglyoxylate:acceptor oxidoreductase was purified and studied. The oxygen-sensitive enzyme reduced both NAD+ and viologen dyes. It was composed of five subunits of approximately 50, 48, 43, 24, and 11.5 kDa; the native mass as determined by gel filtration was 370 kDa, suggesting an alpha2 beta2 gamma2 delta2 epsilon2 composition. Phenylglyoxylate:acceptor oxidoreductase exhibited an ultraviolet/visible spectrum characteristic for an iron-sulfur protein and contained 35 +/- 4 mol Fe, 36 +/- 4 mol acid-labile sulfur, and 1.1 +/- 0.2 mol FAD/mol. The enzyme was specific for phenylglyoxylate (Km 45 microM) and coenzyme A (Km 55 microM); 2-oxoisovalerate was oxidized with 15% of the rate. The turnover number with benzyl viologen at 37 degrees C was 46 s(-1) at the optimal pH of 8. The enzyme catalyzed a NAD(P)H:viologen dye transhydrogenation reaction, NAD(H) being the preferred coenzyme. It also catalyzed an isotope exchange between CO2 and the carboxyl group of the substrate. The data are consistent with the following hypothesis. The enzyme complex consists of a core enzyme of four subunits with the composition alpha2 beta2 gamma2 delta2, as reported for archaeal 2-oxoacid:ferredoxin oxidoreductases; this complex is able to reduce viologen dyes. The holoenzyme contains in addition an epsilon2 unit that catalyzes the transfer of electrons from a small ferredoxin-like subunit of the core complex to NAD+; this unit also catalyzes the transhydrogenase reaction, carries FAD and resembles ferredoxin:NAD(P)+-oxidoreductase.

Amino Acid Sequence↗
PubMed1998

4-Hydroxybenzoyl-CoA reductase (dehydroxylating) from the denitrifying bacterium Thauera aromatica--prosthetic groups, electron donor, and genes of a member of the molybdenum-flavin-iron-sulfur proteins.

4-Hydroxybenzoyl-CoA reductase catalyzes an important reaction in the anaerobic metabolism of phenolic compounds, i.e. the reductive removal of an aromatic hydroxyl group. The prosthetic groups and the natural electron donor of the enzyme were investigated and the genes were cloned and sequenced. The enzyme is a molybdenum-flavin-iron-sulfur protein of subunit composition of alpha2beta2gamma2. It contains approximately 1.3 flavin nucleotide, probably FAD, 1.9 Mo, 15 Fe, and 12.5 acid-labile sulfur. Sequence interpretation suggests that the native enzyme contains two [4Fe-4S] and four [2Fe-2S] clusters. A 9.8-kDa ferredoxin with two [4Fe-4S] clusters functions as the natural electron donor. The genes coding for the three subunits, hcrABC, show high similarities to other molybdenum-flavin-iron-sulfur proteins of the xanthine oxidase family, notably to the three putative 4-hydroxybenzoyl-CoA reductase genes in Rhodopseudomonas palustris. In addition, there are close similarities to three open reading frames (orf) in E. coli. A major difference is the presence of an additional domain in the beta-subunit (HcrB, 35 kDa) probably carrying an additional iron-sulfur cluster. The 82-kDa alpha-subunit (HcrA) contains a Mo-cofactor-binding site. The 17-kDa gamma-subunit (HcrC) harbors two [2Fe-2S] clusters. Upstream of the hcrCAB region, an ORF was found coding for a regulatory protein of the MarR family. Downstream of the hcrCAB region lies an ORF presumably coding for a hydrophobic permease.

Amino Acid Sequence↗
PubMed1998

Identification and characterization of the natural electron donor ferredoxin and of FAD as a possible prosthetic group of benzoyl-CoA reductase (dearomatizing), a key enzyme of anaerobic aromatic metabolism.

Under anoxic conditions most aromatic compounds are metabolized via benzoyl-CoA which becomes reduced by benzoyl-CoA reductase (dearomatizing); this enzyme was recently described in the bacterium Thauera aromatica [Boll, M. & Fuchs, G. (1995) Eur. J. Biochem. 234, 921-933]. It catalyzes the reaction benzoyl-CoA + 2 e- + 2 H+ + 2 MgATP + 2 H2O --> cyclohexa-1,5-diene-1-carboxyl-CoA + 2 MgADP + 2 Pi. The iron-sulfur protein has a native molecular mass of 160-170 kDa and consists of four different subunits. In addition a flavin may be present. The nature of the potential prosthetic group and the natural electron donor were determined. Purified benzoyl-CoA reductase preparations contained 0.25-0.3 mol FAD/mol enzyme. Cells grown anaerobically with aromatic substrates contained a ferredoxin which represented the main, if not the only ferredoxin present. It was purified from 200 g cells with a yield of 60 mg and its N-terminal amino acid sequence was determined. The native molecular mass was 9659 +/- 2 Da as determined by electrospray mass spectrometry. The protein contained 7.6 +/- 0.6 mol iron and 7.6 +/- 1 mol acid-labile sulfur/mol. The ultraviolet-visible spectrum of the protein was typical for ferredoxins with maxima at 280 nm and 390 nm (in the oxidized state). The estimated molar absorption coefficients were 63500 M(-1) cm(-1) at 280 nm and 40500 M(-1) cm(-1) at 390 nm. The difference spectrum between the oxidized and the reduced form had a maximum at 415 nm with delta epsilon415 = 8200 M(-1) cm(-1). 1 mol ferredoxin became reduced/mol dithionite added, suggesting the presence of two [4Fe-4S] clusters. The average midpoint potential of the iron-sulfur clusters was -450 mV. The ferredoxin gene was cloned and sequenced. It was located in a gene cluster coding for enzymes involved in anaerobic aromatic metabolism. The amino acid sequence of the T. aromatica ferredoxin showed high similarities to several other ferredoxins containing 2[4Fe-4S] clusters, e.g. from Clostridia and phototrophic bacteria. The reduced ferredoxin served as electron donor for benzoyl-CoA reduction at a three times higher rate compared with the rate obtained with the artificial electron donor reduced methyl viologen. The turnover number with the natural electron donor of 5 s(-1) can explain the bacterial growth rate with benzoate as substrate. Half-maximal enzyme activity was obtained with 6 microM reduced ferredoxin, at an estimated cellular concentration of 70 microM ferredoxin. Both the low apparent Km value and the turnover number are consistent with the proposed role of ferredoxin in aromatic-ring reduction.

Amino Acid Sequence↗
PubMed1998

[Preoperative diagnosis of a patent foramen ovale: rational use of transthoracic and transesophageal contrast echocardiography].

BACKGROUND: The detection or ruling out of a patent foramen ovale (PFO) can be determined noninvasively by contrast echocardiography (CE). The transesophageal technique is superior to the transthoracic technique regarding sensitivity, whereas the specificity of both methods is equally high. This prospective study shows the rational use of transesophageal CE for the detection of a PFO, in patients without cardiovascular disorders. METHODS: 165 patients (92 female, 73 male, age 48 +/- 18 years) with planned neuro-surgery in a sitting position, underwent CE to rule out a PFO. If the CE was positive, an alternative position was selected in order to avoid a paradoxical air embolism. RESULTS: Initially, a transthoracic CE was performed in all patients resulting in 21 patients (13%) being positive and 39 patients (24%) being negative by sufficient image quality. A transesophageal CE was performed in 96 of the remaining 105 patients (63%). Here, further 25 patients showed a positive CE in the sense of a PFO. The combined use of transthoracic and transesophageal CE revealed a PFO in 46 of 165 patients (28%). CONCLUSION: The use of both, transthoracic and transesophageal CE is an efficient approach to the preoperative detection of a PFO in the sense of quality and economics. Depending upon the image quality, the use of a transesophageal examination could be avoided in one third of the cases.

Adolescent↗
PubMed1998

Phenylacetyl-CoA:acceptor oxidoreductase, a new alpha-oxidizing enzyme that produces phenylglyoxylate. Assay, membrane localization, and differential production in Thauera aromatica.

Anaerobic oxidation of phenylalanine and phenylacetate proceeds via alpha-oxidation of phenylacetyl-CoA to phenylglyoxylate. This four-electron oxidation system was studied in the denitrifying bacterium Thauera aromatica. It is membrane-bound and was solubilized with Triton X-100. The system used dichlorophenolindophenol as an artificial electron acceptor; a spectrophotometric assay was developed. No other products besides phenylglyoxylate and coenzyme A were observed. The enzyme was quite oxygen-insensitive and was inactivated by low concentrations of cyanide. Enzyme activity was induced under denitrifying conditions with phenylalanine and phenylacetate, it was low in cells grown with phenylglyoxylate, and it was virtually absent in cells grown with benzoate and nitrate or after aerobic growth with phenylacetate.

Anaerobiosis↗
PubMed1998

Differential induction of enzymes involved in anaerobic metabolism of aromatic compounds in the denitrifying bacterium Thauera aromatica.

Differential induction of enzymes involved in anaerobic metabolism of aromatic substrates was studied in the denitrifying bacterium Thauera aromatica. This metabolism is divided into (1) peripheral reactions transforming the aromatic growth substrates to the common intermediate benzoyl-CoA, (2) the central benzoyl-CoA pathway comprising ring-reduction of benzoyl-CoA and subsequent beta-oxidation to 3-hydroxypimelyl-CoA, and (3) the pathway of beta-oxidation of 3-hydroxypimelyl-CoA to three acetyl-CoA and CO2. Regulation was studied by three methods. 1. Determination of protein patterns of cells grown on different substrates. This revealed several strongly substrate-induced polypeptides that were missing in cells grown on benzoate or other intermediates of the respective metabolic pathways. 2. Measurement of activities of known enzymes involved in this metabolism in cells grown on different substrates. The enzyme pattern found is consistent with the regulatory pattern deduced from simultaneous adaptation of cells to utilisation of other aromatic substrates. 3. Immunological detection of catabolic enzymes in cells grown on different substrates. Benzoate-CoA ligase and 4-hydroxybenzoate-CoA ligase were detected only in cells yielding the respective enzyme activity. However, presence of the subunits of benzoyl-CoA reductase and 4-hydroxybenzoyl-CoA reductase was also recorded in some cell batches lacking enzyme activity. This possibly indicates an additional level of regulation on protein level for these two reductases.

Acyl Coenzyme A↗
PubMed1998

Single-breath diffusing capacities for NO, CO and C18O2 in rabbits.

Nitric oxide (NO) has been introduced recently for studying alveolar-capillary gas transfer. Due to extremely fast reaction kinetics for the association of NO with haemoglobin, pulmonary NO uptake is expected to depend only on diffusion, whereas in the case of carbon monoxide (CO) or oxygen-labelled carbon dioxide (C18O2) the alveolar-capillary transfer is, in addition, known to depend on a blood uptake component. To provide further data for NO, CO and C18O2, we determined the pulmonary diffusing capacities (DL) for the indicator gases mentioned, performing single-breath manoeuvres on ten rabbits. The inspired gas mixtures contained 0.05% NO and/or 0. 2% CO or 1% C18O2 in nitrogen. Applying respiratory mass spectrometry to the expirates we obtained the following mean +/- SD values: DL,NO/DL,CO = 3.55 +/- 0.4, DL,C18O2/DL,NO = 6.0 +/- 0.6, DL, C18O2/DL,CO = 21.4 +/- 2.5. Graham's law predicts DL ratios of 1.9 for NO/CO, 12 for C18O2/NO, and 23 for C18O2/CO. Thus we equally underestimated the predicted DL ratios for C18O2/NO and CO/NO by a factor of approximately 0.5. From this, and by excluding significant interactions between the indicator gases and lung tissues, we conclude that the closest approximation of the diffusive component of DL is indeed obtained by using NO.

Animals↗
PubMed1998

Impact of zinc supplementation on persistent diarrhoea in malnourished Bangladeshi children.

To evaluate the impact of zinc supplementation on the clinical recovery and body weight of children with persistent diarrhoea, a randomized, double-blind, controlled trial was conducted in 190 children with persistent diarrhoea aged between 3 and 24 months. Children were randomly allocated to receive either zinc (20 mg d(-1)) syrup with multivitamin (2 x RDA) or multivitamin alone in three divided daily doses for 2 weeks. The trial was conducted in a diarrhoeal disease hospital in Dhaka, Bangladesh. Duration until clinical recovery (d), impact on body weight and serum zinc level after 2 weeks of zinc supplementation were recorded. The duration of illness was significantly reduced (33%) with zinc supplementation among children who were underweight (< or =70% wt/age, p = 0.03). Supplemented male children also had a significant reduction (27%) in duration for recovery compared with unsupplemented children (p = 0.05). From baseline to convalescence, zinc-supplemented children maintained their serum zinc concentration (13.4 vs 13.6 micromol l(-1)), whereas unsupplemented children had a decrease in serum zinc after the 2 weeks of diarrhoea (13.6 vs 11.8 micromol l(-1),p < 0.03). The mean body weight of the children in the supplemented group was maintained (5.72 vs 5.70 kg, p = 0.62) during hospitalization, unlike that of the control group, in which there was a reduction in body weight (5.75 vs 5.67 kg, p = 0.05). Five children in the unsupplemented group and one child in the zinc-supplemented group died during the 2 weeks of supplementation (p = 0.06). Zinc supplementation in persistent diarrhoea significantly reduced the length of the recovery period in malnourished children and prevented a fall in body weight and serum zinc concentration, indicating that zinc is a beneficial therapeutic strategy in this high-risk childhood illness.

Bangladesh↗
PubMed1998

Pulmonary diffusing capacities for oxygen-labeled CO2 and nitric oxide in rabbits.

We determined the pulmonary diffusing capacity (DL) for 18O-labeled CO2 (C18O2) and nitric oxide (NO) to estimate the membrane component of the respective gas conductances. Six anesthetized paralyzed rabbits were ventilated by a computerized ventilatory servo system. Single-breath maneuvers were automatically performed by inflating the lungs with gas mixtures containing 0.9% C18O2 or 0.05% NO in nitrogen, with breath-holding periods ranging from 0 to 1 s for C18O2 and from 2 to 8 s for NO. The alveolar partial pressures of C18O2 and NO were determined by using respiratory mass spectrometry. DL was calculated from gas exchange during inflation, breath hold, and deflation. We obtained values of 14.0 +/- 1.1 and 2.2 +/- 0.1 (mean value +/- SD) ml.mmHg-1.min-1 for DL(C18O2) and Dl(NO), respectively. The measured DL(C18O2)/DL(NO) ratio was one-half that of the theoretically predicted value according to Graham's law (6.3 +/- 0.5 vs. 12, respectively). Analyses of the several mechanisms influencing the determination of DL(C18)2 and DL(NO) and their ratio are discussed. An underestimation of the membrane diffusing component for CO2 is considered the likely reason for the low DL(C18O2)/DL(NO) ratio obtained.

Animals↗
PubMed1998

Detection of Shigellae from stools of dysentery patients by culture and polymerase chain reaction techniques.

In Bangladesh, the isolation rates of Shigella spp. range from 11% to 12% by the conventional culture technique. Since the sensitivity of this technique is low, the polymerase chain reaction (PCR) technique was used for detecting small number of Shigellae from patients' stools. Sensitivity and specificity of the two techniques were also compared. Stool samples were collected from 41 patients with dysentery who attended the Clinical Research and Service Centre of the ICDDR,B: Centre for Health and Population Research. All stool specimens were directly plated onto MacConkey, Salmonella-Shigella, Xylose lysin deoxycholate and Hectoen enteric agar media, and Shigellae were detected following standard procedures. DNA was extracted from the stool samples, and the target sequence of invasive plasmid antigen (ipa)H locus was amplified by PCR with 130 ng each of two primers (primer H8 [5'-GTTCCTTGACCGCCTTTCCGATAC-3'] and primer H15 [5'-GCCGGTCAGCCACCCTA-3']) following standard procedures. The amplified product was hybridized using an ipaH probe. The isolation rates of Shigella dysenteriae type 1, S. flexneri, S. sonnei, and S. boydii were, respectively, 17.1%, 19.5%, 4.9% and 2.4% by the conventional method. The results of the PCR technique showed that 700 bp fragment was generated in 18 of the 18 culture-positive and in 7 of the 23 culture-negative stools. One hundred twenty-three strains of Escherichia coli were also tested by PCR for identifying the enteroinvasive E. coli, but none of them yielded any positive result. This study showed that the sensitivity of the culture technique is 72% and specificity is 100%, when the PCR technique was considered as gold standard. Therefore, the PCR may be considered a more sensitive and specific technique than the conventional culture technique and has the potential to be employed in routine diagnosis of dysentery in clinical centres as well as in epidemiologic studies.

Bacteriological Techniques↗
PubMed1998

Doppler color-flow imaging: screening of a patent foramen ovale in children scheduled for neurosurgery in the sitting position.

A patent foramen ovale (PFO) is the most common cause of paradoxical air embolism during neurosurgical procedures in the posterior fossa in the sitting position in both adults and children. To detect right-to-left shunting, we performed Doppler color-flow imaging preoperatively in 30 children scheduled for neurosurgical procedures in the sitting position. A PFO was diagnosed on the basis of color alterations indicating an immediate blood shunt through a PFO. Six of 30 children (20%) had a PFO; in 4 of these children the sitting position then was avoided, and 2 children were operated on in a special supine position with minimal elevation of the head. Venous air embolism occurred in 9 of 24 (37%) children operated on in the sitting position and in none of the 6 children operated on in a nonsitting position. We conclude that Doppler color-flow mapping could be a useful noninvasive technique to screen children scheduled for neurosurgery in the sitting position for the presence of a PFO.

Adolescent↗
PubMed1997

Benzoyl-CoA reductase (dearomatizing), a key enzyme of anaerobic aromatic metabolism. A study of adenosinetriphosphatase activity, ATP stoichiometry of the reaction and EPR properties of the enzyme.

An enzyme was recently described, benzoyl-CoA reductase (dearomatizing), which catalyses the ATP-driven reduction of the aromatic ring of benzoyl-CoA yielding a non-aromatic CoA thioester, ADP and phosphate [Boll, M. & Fuchs, G. (1995) Eur. J. Biochem. 234, 921-933]. The 170-kDa enzyme consists of four different subunits and contains approximately 12 Fe and acid-labile sulfur/mol. Benzoyl-CoA reductase exhibits ATPase activity in the absence of substrate. It is shown that only the reduced form of this iron-sulfur protein has ATPase activity. ATPase activity is reversibly lost when the enzyme is oxidized by thionine; reduction of the enzyme fully restores ATPase and ring-reduction activity. 2 mol ATP are hydrolyzed/2 mol electrons transferred in the course of the reaction. The product ADP acts as competitive inhibitor (Ki = 1.1 mM) for ATP in benzoyl-CoA reduction; ADP inhibits ATPase activity to the same extent as ring-reduction activity. EPR investigation of the dithionite-reduced enzyme suggested the presence of two separate [2Fe-2S] clusters and two interacting [4Fe-4S] clusters. Addition of MgATP to the reduced enzyme resulted in a new isotropic signal at g = 5.15 and a weak signal at g = 12; in controls with MgADP only a minor signal at g = 5.15 was observed. The positions, shapes and temperature dependencies of these MgATP-induced signals are indicative for excited states of a S = 7/2 spin multiplet. The [2Fe-2S] signals were not affected by ATP, but one of the [4Fe-4S] clusters became slowly oxidized. Addition of both benzoyl-CoA and MgATP resulted in a major oxidation of the iron-sulfur clusters accompanied by the appearance of some minor signals of unknown origin in the g = 2.037-1.96 region. Neither the benzoyl-CoA plus MgATP-oxidized nor the thionine-oxidized enzyme showed the ATP-dependent formation of the high-spin signals of the reduced enzyme. At present we hypothesize that the S = 7/2 signal is due to an ATP-induced change of one of the [4Fe-4S] clusters. The data suggest that hydrolysis of MgATP is required to activate the enzyme; in the absence of substrate the energy involved in this activation dissipates. MgATP-driven formation of this excited state of the reduced enzyme rather than transfer of electrons from the reduced enzyme to the aromatic substrate appears to be the rate-limiting step in the catalytic cycle. We suggest that the excited state is required to overcome the high activation energy associated with the loss of the aromatic character and/or to render ring reduction irreversible.

Acyl Coenzyme A↗
PubMed1997

[Parkinson disease--problems in long-term treatment. Dopamine agonists optimize L-dopa therapy].

In a 59-year-old male with a 10 year history of Parkinson's disease, progressive movement disorders occurred under medical treatment (end-of-dose akinesia and peak-dose dyskinesia). Thereupon his treatment was changed to a combination of L-dopa/ decarboxylase inhibitor administered during the day in 5 fractions, and additionally a slow-release dopa preparation given on retiring for the night. At the same time, the patient received the dopamine agonist lisuride. While the patient was hospitalized for surgery, his anti-parkinsonism regimen was initially stopped and then continued in changed form. In the following weeks he experienced a drastic impairment of mobility and, in particular, suffered pronounced nocturnal hypokinetic events. A second period of hospitalization became necessary, a complex medical therapeutic regimen similar to the previously successful combination was established. This resulted in satisfactory mobility, and the patient was able to go back to work.

Antiparkinson Agents↗
PubMed1997

Anaerobic metabolism of aromatic compounds.

Aromatic compounds comprise a wide variety of low-molecular-mass natural compounds (amino acids, quinones, flavonoids, etc.) and biopolymers (lignin, melanin). They are almost exclusively degraded by microorganisms. Aerobic aromatic metabolism is characterised by the extensive use of molecular oxygen. Monoxygenases and dioxygenases are essential for the hydroxylation and cleavage of aromatic ring structures. Accordingly, the characteristic central intermediates of the aerobic pathways (e.g. catechol) are readily attacked oxidatively. Anaerobic aromatic catabolism requires, of necessity, a quite different strategy. The basic features of this metabolism have emerged from studies on bacteria that degrade soluble aromatic substrates to CO2 in the complete absence of molecular oxygen. Essential to anaerobic aromatic metabolism is the replacement of all the oxygen-dependent steps by an alternative set of novel reactions and the formation of different central intermediates (e.g. benzoyl-CoA) for breaking the aromaticity and cleaving the ring; notably, in anaerobic pathways, the aromatic ring is reduced rather than oxidised. The two-electron reduction of benzoyl-CoA to a cyclic diene requires the cleavage of two molecules of ATP to ADP and P1 and is catalysed by benzoyl-CoA reductase. After nitrogenase, this is the second enzyme known which overcomes the high activation energy required for reduction of a chemically stable bond by coupling electron transfer to the hydrolysis of ATP. The alicyclic product cyclohex-1,5-diene-1-carboxyl-CoA is oxidised to acetyl-CoA via a modified beta-oxidation pathway; the ring structure is opened hydrolytically. Some phenolic compounds are anaerobically transformed to resorcinol (1,3-dihydroxybenzene) or phloroglucinol (1,3,5-trihydroxybenzene). These intermediates are also first reduced and then as alicyclic products oxidised to acetyl-CoA. This review gives an outline of the anaerobic pathways which allow bacteria to utilize aromatics even in the absence of oxygen. We focus on previously unknown reactions and on the enzymes characteristic for such novel metabolism.

Acyl Coenzyme A↗