Pre­cious Met­als

by Elio

Life should be like the pre­cious met­als, weigh much in lit­tle bulk
—Seneca (Ro­man philoso­pher, mid-1st cen­tury AD)

Now that news of the ar­senic-eat­ing bac­te­ria has sat­u­rated cy­ber­space, the air­waves, and even old-fash­ioned newsprint, we step back to raise a larger ques­tion: Why have so few el­e­ments from the pe­ri­odic ta­ble made it into liv­ing things? You sel­dom hear about any­thing past the first few rows in the ta­ble. Turns out this is a gross over­sight. Many more el­e­ments, pre­vi­ously un­sus­pected, are to be found in a large num­ber of met­al­lo­pro­teins. So, move over, ar­senic and make room for other el­e­ments.

One size might not fit all. Source

Un­til re­cently, the topic of metal ion co­fac­tors and met­al­lo­pro­teins has been some­thing of a bio­chem­i­cal stepchild. For sure, some re­searchers have avidly pursed it. How­ever, in most cases, the pres­ence of metal was re­vealed serendip­i­tously af­ter the pro­tein was pu­ri­fied.

Source

But what if one set out to cast a wide net for met­al­lo­pro­teins? The au­thors of a re­cent pa­per did just that by ex­am­in­ing the pro­teins of the ar­chaeon Py­ro­coc­cus fu­rio­sus (a su­per-hy­per­ther­mophile that the au­thors call "a pro­to­typ­i­cal mi­crobe," an in­ter­est­ing point of view that we salute). They found sev­eral hun­dred such pro­teins con­tain­ing an un­ex­pected as­sort­ment of met­als. Analy­sis of two ad­di­tional or­gan­isms, Es­cherichia coli and Sul­folobus sol­fa­tar­i­cus, re­vealed the species-spe­cific as­sim­i­la­tion of yet more un­ex­pected met­als — cad­mium, ar­senic(!), ura­nium, and nickel in E. coli, and both tin and an­ti­mony in S.solfataricus (see Fig.).

To en­sure that the met­als were not con­t­a­m­i­nants, the re­searchers went to great lengths, in­clud­ing pu­ri­fy­ing pro­teins by a com­bi­na­tion of chro­mato­graphic tech­niques. They then used a fancy and highly-sen­si­tive type of mass spec­trom­e­try called in­duc­tively cou­pled plasma mass spec­trom­e­try to de­ter­mine the metal con­tent of the pro­teins. To­gether these tech­niques al­lowed for much faster and more pre­cise iden­ti­fi­ca­tion of met­al­lo­pro­teins than had been pre­vi­ously pos­si­ble. Even the ex­ist­ing bioin­for­mat­ics pro­gram called In­ter­Pro-Metal had turned out to be of only lim­ited help.

One-third of all pro­teins are "met­allo-pro­teins", che­mical com­bi­na­tions of pro­tein atoms (car­bon, ni­tro­gen, oxy­gen, hy­dro­gen, sul­fur) with ions of met­als such as iron, cal­cium, cop­per, and zinc. Source (dead link in 2026)

Us­ing these tech­niques to char­ac­ter­ize the chro­mato­graph­i­cally pu­ri­fied pro­teins of P. fu­rio­sus they found 343 metal peaks among their pro­tein frac­tions, 158 of which did not match any known met­al­lo­pro­tein. Some of these unas­signed peaks con­tained met­als known to be present in pro­teins of this or­gan­ism (e.g., cobalt, iron, nickel, tung­sten, and zinc in about half of the peaks) while oth­ers pos­sessed un­sus­pected met­als (e.g., lead, man­ganese, molyb­de­num, ura­nium, and vana­dium in most of the other half of the peaks). In to­tal, the au­thors found that this or­gan­ism con­tains 21 of the 53 met­als an­a­lyzed. Most abun­dant were met­al­lo­pro­teins con­tain­ing iron and zinc (97% of the to­tal). Note that no ex­tra met­als had been added to the growth medium but they were surely present in trace amounts. Tak­ing a page from the re­cent re­port on ar­senic us­age by a bac­te­ria, grow­ing the or­gan­isms in in­creas­ing amounts of these met­als may lead to in­ter­est­ing re­sults. With el­e­men­tary at­ten­tion to el­e­men­tal analy­sis and in­ter­pre­ta­tion, this should not lead to con­tro­versy.

Why should we care that these pro­teins con­tain un­ex­pected met­als? The au­thors il­lus­trate sev­eral rea­sons, such as the find­ing of zinc and iron-sul­fur in DNA re­pair pro­teins that are rel­e­vant to hu­man can­cers and the ob­ser­va­tion that pro­teins made by re­com­bi­nant tech­nol­ogy may be lack­ing es­sen­tial met­als. One can add much to this list. But the mes­sage is a gen­eral one: there is much more to the world of met­al­lo­pro­teins than we had en­vis­aged.

Ref­er­ence

Cvetkovic A, Menon AL, Thorg­ersen MP, Scott JW, Poole FL 2^nd, et al. (2010). Mi­cro­bial met­al­lo­pro­teomes are largely un­char­ac­ter­ized. Na­ture, 466 (7307), 779−782. PMID 20639861