Microbial methylation of metalloids: arsenic, antimony, and bismuth

Abstract

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.

FIG. 1.

Examples of arsenolipids. (A) O-Phosphatidyltrimethylarsonium lactic acid; (B) an arsenoribofuranoside. Several variations on this structure are observed. In each case, R is a fatty acyl residue.

FIG. 2.

Typical reactions of the Challenger mechanism. The top line indicates a mechanism for the reduction, As(V) → As(III), resulting in an unshared pair of electrons on As. Structures are as follows: R₁ = R₂ = OH, arsenate; R₁ = CH₃, R₂ = OH, methylarsonate; R₁ = R₂ = CH₃, dimethylarsinate. For reduction of trimethylarsine oxide to trimethylarsine, the process is a little different. Following proton addition, the structure H-O-As⁺(CH₃)₃ reacts with hydride ion leading to elimination of H₂O. The bottom line indicates the methylation of an As(III) structure with SAM [shown in abbreviated form as CH₃-S⁺-(C)₂]. A proton is released and SAM is converted to S-adenosylhomocysteine [abbreviated form, S-(C)₂].

FIG. 3.

Challenger mechanism for the conversion of arsenate to trimethylarsine. (A) Arsenate; (B) arsenite; (C) methylarsonate; (D) methylarsonite; (E) dimethylarsinate; (F) dimethylarsinite; (G) trimethylarsine oxide; (H) trimethylarsine. The top line of structures shows the As(V) intermediates. The vertical arrows indicate the reduction reactions to the As(III) intermediates (bottom line), and the diagonal arrows indicate the methylation steps by SAM (see Fig. 2 for details of the reduction and methylation processes).

FIG. 4.

Changes in oxidation numbers on As and C during methylation according to Hanselmann's method (117). Abbreviations: Ox, oxidation number; E.N., electronegative (than).

FIG. 5.

Expanded version of the Challenger mechanism. This mechanism, proposed for C. humiculus, indicates roles for components both in the cells themselves and in the culture medium. The double vertical lines indicate cell walls. (A) Phosphate transport system; (B) thiols and/or dithiols; (C) active transport system; (D) active/passive transport; (E) passive diffusion. Abbreviations: MMA^V, methylarsonic acid; DMA, dimethylarsinic acid; TMAO, trimethylarsine oxide. This diagram is redrawn from scheme 2 of reference .

FIG. 6.

Possible mechanism for formation of a “cryptocarbanion” from a methyl cobalamin. E indicates an enzyme containing two SH groups (209, 210).