Ronald Bentley

Microbial Methylation of Metalloids: Arsenic, Antimony, and Bismuth

SUMMARY A significant 19th century public health problem was that the inhabitants of many houses containing wallpaper decorated with green arsenical pigments experienced illness and death. The problem was caused by certain fungi that grew in the presence of inorganic arsenic to form a toxic, garlic-odored gas. The garlic odor was actually put to use in a very delicate microbiological test for arsenic. In 1933, the gas was shown to be trimethylarsine. It was not until 1971 that arsenic methylation by bacteria was demonstrated. Further research in biomethylation has been facilitated by the development of delicate techniques for the determination of arsenic species. As described in this review, many microorganisms (bacteria, fungi, and yeasts) and animals are now known to biomethylate arsenic, forming both volatile (e.g., methylarsines) and nonvolatile (e.g., methylarsonic acid and dimethylarsinic acid) compounds. The enzymatic mechanisms for this biomethylation are discussed. The microbial conversion of sodium arsenate to trimethylarsine proceeds by alternate reduction and methylation steps, with S-adenosylmethionine as the usual methyl donor. Thiols have important roles in the reductions. In anaerobic bacteria, methylcobalamin may be the donor. The other metalloid elements of the periodic table group 15, antimony and bismuth, also undergo biomethylation to some extent. Trimethylstibine formation by microorganisms is now well established, but this process apparently does not occur in animals. Formation of trimethylbismuth by microorganisms has been reported in a few cases. Microbial methylation plays important roles in the biogeochemical cycling of these metalloid elements and possibly in their detoxification. The wheel has come full circle, and public health considerations are again important.

Role of sulfur chirality in the chemical processes of biology

Chiral structures profoundly influence chemical and biological processes. While chiral carbon biomolecules have received much attention, chirality is also possible in certain sulfur compounds; just as with carbon, there can be differences in the physiological behavior of chiral sulfur compounds. For instance, one drug enantiomer, Nexium (esomeprazole, a chiral sulfoxide), is used for its superior clinical properties as a proton pump inhibitor over the racemic mixture, Prilosec (Losec, omeprazole). This critical review introduces sulfur stereochemistry and nomenclature, and provides a comprehensive approach to chiral sulfur compounds and their enzymatic reactions in general and secondary metabolism. The major structural types of biological interest are sulfonium salts, sulfoxides, and sulfoximines. (103 references).

Seeing red : The story of prodigiosin

Publisher Summary S. marcescens has played an important role in the history of bacterial taxonomy, in research on the transmission of bacterial aerosols, in the study of emerging nosocomial infections, and in the understanding of secondary metabolite biosynthesis. The prodigiosin pigments have intrigued organic chemists and pharmacologists, and play roles in the treatment of infectious diseases such as malaria, and perhaps as immunosuppressant agents. Undecylprodiginine played an important role in the first cloning of a gene, playing a defined role in the biosynthesis of an antibiotic. An O-methyltransferase gene was isolated by complementation and the color of undecylprodiginine was used as the selectable phenotype. The regulation of prodigiosin biosynthesis is complex, being influenced by increased glucose levels and decreased by increased phosphate level. The antibiotic resistance of many strains of S. marcescens is a serious problem with rapid horizontal transfer of drug resistance by plasmids.

From miso, saké and shoyu to cosmetics: a century of science for kojic acid

This article reviews the curious history of kojic acid, discovered as a fungal natural product in 1907. It was one of the first secondary metabolites to have its biosynthetic pathway studied by the isotope tracer technique, and, more recently, has been of interest as a skin lightening agent. There are 112 references.

Geosmin and methylisoborneol biosynthesis in streptomycetes: Evidence for an isoprenoid pathway and its absence in non-differentiating isolates

Geosmin, 1, (trans-1 ,lOdimethyl-trans-9-decalol) and the 2-methyl derivative of isoborneol, 2, (1,2,7,7tetramethyl-exo-bicycle [2.2.l]heptan-2-01) are volatile metabolites of various Streptomycetes, algae, and fungi [ 11. Geosmin in particular has an intense ‘earthy’ or ‘musty’ odor. Both metabolites have caused odor and taste problems in water supplies [2] and foods but geosmin is important for the flavour of beets [3]. Despite the problems for water supplies, there is almost no biosynthetic information for these materials. However, aerial mycelium negative (amy-) isolates of Streptomyces alboniger, S. scabies, and S. violaceous-ruber failed to produce an earthy odor; the uncharacterized material was assumed to be geosmin [4]. We have used radio-gas chromatography to investigate the biosynthesis of geosmin and 2-methylisoborneol and have obtained amyisolates of S. sulfureus and S. antibioticus which produce neither metaboiite.

What's in a name?―Microbial secondary metabolism

Publisher Summary This chapter discusses microbial secondary metabolism. Of the prodigious number of carbon compounds, many are materials produced by living organisms. They are termed “natural products” Natural products constitute a very large and diverse group of compounds that are hard to characterize. This chapter focuses on “secondary metabolites.” The chapter explored what secondary metabolites are; origin of this term; and the use of secondary metabolites in biological sciences. Modern organic chemistry began with the isolation and characterization of certain compounds from human body fluids and from plant and animal tissues. In the second half of the nineteenth century, the number of known metabolites increased almost exponentially. To organic chemists, these strange metabolites were simply “natural products” providing never ending challenges of structure determination and total synthesis. With the exception of pigments, the chemical diversity expressed in secondary metabolism is less obvious and therefore, more mysterious. This represents the beguiling and beautiful manifestations of genotypic differentiation that species have perfected during their evolutionary history.

[7] Gas chromatography of carbohydrates

Publisher Summary This chapter discusses the preparation of gas chromatography of carbohydrates. Analyses of carbohydrates by gas–liquid partition chromatography are carried out with volatile derivatives of the substances under investigation. Extensive studies are made of the chromatographic behavior of derivatives such as O -methyl ethers, O -acetyl esters, O -trimethylsilyl (TMS) ethers, and various acetals and ketals. The separations can be obtained with any of these modified forms of carbohydrates, the volatilities of which are generally sufficient for gas chromatography under a wide variety of operating conditions. The reaction yielding a derivative must be rapid and quantitative with any carbohydrate; preferably it should be carried out at room temperature, and must be suitable for use over a wide range of concentration of the starting material. Nonpolar derivatives are usually less reactive than polar ones and are preferred for quantitative determinations. Packed columns or open tubular columns may be operated isothermally or with temperature programming. A short packed column containing a low percentage of dimethylsilicone gum (SE-30) is the most useful, all-purpose column for the determination of carbohydrates by gas chromatography.

Different roads to discovery; Prontosil (hence sulfa drugs) and penicillin (hence β-lactams)

The important chemotherapeutic agents, Prontosil and pentenylpenicillin (penicillin F), were investigated initially by two men, Domagk and Fleming, who had been influenced by the horrendous wound infections of World War I. The very different pathways leading to their development and to that of the successor antibacterials (sulfa drugs, further penicillins, semi-synthetic penicillins), including the role played by patents, are discussed.

Diastereoisomerism, contact points, and chiral selectivity: a four-site saga.

In biology, chiral recognition usually implies the ability of a protein, such as an enzyme or a drug receptor, to distinguish between the two enantiomeric forms of a chiral substrate or drug. Both diastereoisomerism and specific contacts between enzyme/receptor and substrate/drug are necessary. The minimum requirement is for four contact points including four nonplanar atoms (or groups of atoms) in both probe and target. The molecular models described by Easson and Stedman and by Ogston require three binding sites in a plane. A modified model with three binding sites in three dimensions is described. Under certain circumstances this model allows binding of both enantiomeric forms of a substrate or a drug. Enantiomer superposition of two enantiomers at an active site occurs in some specific cases (e.g., phenylalanine ammonia-lyase, isocitrate dehydrogenase) and is likely in others. The nature of enantiomer binding to racemase enzymes is discussed.

Conformational aspects of the reaction mechanisms of polysaccharide lyases and epimerases.

During the biosynthesis of some polysaccharides (e.g. alginic acid [l] and heparin [2]) pyranosyluronate residues undergo epimerization at C-5 after incorporation into the polymer chain. In the case of heparin, the enzyme heparosan-llrsulfate D-glucuronosyl 5-epimerase (EC 5.1.3.17) catalyzes the exchange of hydrogen atoms at C-5 with solvent protons. Hence, it was postulated that the initial step of the epimerization required abstraction of the C-5 proton by a nucleophilic group of the enzyme to form a carbanion; the carbanion could regain a proton either with retention or inversion of configuration [3,4]. These polysaccharides may also be modified by the action of lyases. Thus, in the modification of alginic acid, a ‘mannuronate lyase’ (alginate lyase, EC 4.2.2.3) degrades the polymer to oligosaccharides containing 4-deoxy-L-erythro-hex-4-ene pyranosyluronate at the non-reducing end. Gacesa [5] has proposed an extension of the carbanion mechanism to the lyase enzymes. For the lyase