Deadly Pret­zels

Mid-week...the third of five in­stall­ments cel­e­brat­ing the Week of the Fungi on STC.

by Elio

A bou­quet of poi­so­nous mush­rooms. Num­ber 3 is Amanita phal­loides. From McIl­vaine, C. 1900. One Thou­sand Ameri­can Fungi. The Bowen-Mer­rill Com­pany, In­di­anapo­lis

Nasty stuff, those tox­ins re­spon­si­ble for the tox­i­c­ity of deadly poi­so­nous Amanita mush­rooms. They are pret­zel-shaped, bi­cyclic octa- and hep­tapep­tides known as ama­toxins and phal­lo­tox­ins. One of them, α‑amanitin, is fa­miliar to many as a handy reagent for in­hibit­ing RNA Po­lymerase II in the lab. An­other one, phal­loidin, binds to actin and in­hibits its de­poly­mer­iza­tion. Made flu­o­res­cent, it's a con­ve­nient way to stain for actin. Phal­lo­tox­ins are not ef­fec­tive by mouth be­cause they are poorly ab­sorbed. Aman­itins are re­spon­si­ble for most of the cases of se­ri­ous mush­room poi­son­ing, in­clud­ing most fa­tal­i­ties. In­ci­den­tally, these are not ab­sorbed all that fast ei­ther. Symp­toms don't usu­ally be­come ap­par­ent for 12–24 hours af­ter in­ges­tion so if you get sick soon af­ter eat­ing a wild mush­room, it wasn't a deadly Amanita and you'll likely be OK by the next day. Those sto­ries about keel­ing over right af­ter a great mush­room meal are fic­tions.

Struc­tures of α‑amanitin (A) and phalla­cidin (B). Source

How are these odd-look­ing, highly-mod­i­fied pep­tides made? There are two ba­sic meth­ods used by var­i­ous or­gan­isms to make their own par­tic­u­lar pep­tides. One way is to start with a "nor­mal" pro­tein syn­the­sized us­ing mRNA and ri­bo­somes, cleave off a short sec­tion, and then mod­ify it. The other is en­zy­mat­i­cally, em­ploy­ing ded­i­cated non­ri­bo­so­mal pep­tide syn­thetases. Some pep­tides are made one way, some the other. Many bac­terial and an­i­mal pep­tides are made us­ing ri­bo­somes, but un­til re­cently all known cyclic pep­tides in fungi were the prod­uct of pep­tide syn­thetases. These mush­room tox­ins, it turns out, are the ex­cep­tion, be­ing the cleav­age prod­uct of pro­teins. We know this be­cause scrutiny of the genome of one of the deadly aman­i­tas, A. bispori­ge­ra, re­vealed genes for two of these tox­ins. These tox­ins are syn­the­sized as pro­pro­teins 34 or 35 amino acids long and then cleaved by a pro­lyl oligopep­ti­dase. These genes are found in other poi­so­nous species but not in 12 harm­less rel­a­tives. (Not all aman­i­tas are poi­so­nous; some are ac­tu­ally prized ed­i­bles. But please, un­til you know for sure who is who, stay away from them all.)

What good does this for to the poor schnook who ate poi­so­nous mush­rooms? Prob­a­bly not much.

 

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