pyrrolysine: the 22nd standard amino acid???

 

Source: Wikipedia

The world is constantly changing, altering our understanding from past textbooks. The nine planets became eight, twelve pairs of cranial nerves are now thirteen, and the discovery of selenocysteine increased the standard protein amino acids from twenty to twenty-one. However, the discovery of pyrrolysine in archaea and some bacteria in 2002 once again challenged the composition of standard protein amino acids. Some scientists argue that pyrrolysine should be considered the twenty-second amino acid, while others disagree; after all, only methane-producing archaea and some bacteria (including E. coli) use pyrrolysine.

In 2002, scientists discovered pyrrolysine at the active site of methyltransferase in Methanosarcina barkeri. Later, pyrrolysine was found in many methyltransferases; its function in enzymes may be to help adjust the position of methyl groups for reaction with cofactors. Unlike hydroxyproline, pyrrolysine has a genetic code, UAG. Readers might exclaim: Wait! Isn't UAG one of the stop codons? Yes, it is. However, like selenocysteine using UGA, pyrrolysine's use of UAG requires special equipment.

Microorganisms capable of using pyrrolysine carry a special transfer RNA (tRNA) that bears pyrrolysine and has an anticodon to recognize UAG. Moreover, this unique tRNA has its own dedicated aminoacyl-tRNA synthetase (aaRS) responsible for attaching pyrrolysine. Pyrrolysine is synthesized from two lysines and, due to its pyrrolidine structure (see proline), it has the prefix "pyrro-" in its name.

The microbial world is fascinating, and the microorganisms we can cultivate in laboratories likely represent only a small fraction of all microbes. Perhaps in the future, with a better understanding of microorganisms and deep-sea life, we might discover more unique amino acids, and the list of standard protein amino acids may grow even longer!

References:

Wikipedia. Pyrrolysine.

Srinivasan, G; James, C. M.; Krzycki, J. A. 2002. Pyrrolysine encoded by UAG in Archaea: charging of a UAG-decoding specialized tRNA. Science. 296 (5572): 1459–1462. doi:10.1126/science.1069588

吡咯離胺酸（pyrrolysine）：第二十二個標準蛋白質氨基酸？！

吡咯離氨酸。圖片來源：Wiki

這個世界一直在變動，改變我們過去在教科書上的認知；九大行星變成八大行星、十二對腦神經現在成了十三對、而硒半胱氨酸（selenocysteine）的發現，也讓標準蛋白質氨基酸由二十個增加到二十一個。

但是，2002年在古菌（archaea）以及一些細菌裡發現的吡咯離氨酸（Pyrrolysine），再度挑戰到底標準蛋白質氨基酸的組成。有些科學家據此認為吡咯離氨酸應該是第二十二個氨基酸，有些科學家則不認同；畢竟，只有產甲烷的古菌以及一些細菌（包括大腸桿菌）會使用吡咯離氨酸。

在2002年，科學家們在巴氏甲烷八疊球菌（Methanosarcina barkeri）的甲基轉移酶（methyl-transferase）的活化位址發現了吡咯離氨酸。後來發現許多的甲基轉移酶都可以找到吡咯離氨酸；它在酵素裡的功能可能是協助酵素把甲基的位置調整好，好讓輔因子可以跟甲基反應。

與羥脯氨酸（hydroxyproline）不同的是，吡咯離氨酸是有遺傳密碼的，它的遺傳密碼是UAG。讀者看到這裡可能會說：等一下！UAG不是終止密碼之一嗎？是的。不過，就像硒半胱氨酸使用UGA一樣，吡咯離氨酸使用UAG也需要有特別的裝備。能使用吡咯離氨酸的微生物們都帶有一個特別的轉移RNA（tRNA，transfer RNA），這個轉移RNA帶有吡咯離氨酸、且它的反密碼就是用來辨認UAG的。而且，這麼特別的轉移RNA，它也有專屬的氨酰-tRNA合成酶（aminoacyl-tRNA synthetase，簡稱aaRS）來負責把吡咯離氨酸加上去。

吡咯離氨酸是由兩個離氨酸合成的，因為含有吡咯烷（pyrrolidine）的結構（請參考脯氨酸 proline），所以名字裡面加上了pyrro-這個字首。

微生物是個奇妙的世界，我們在實驗室能養出來的微生物，大概只佔全體微生物的小部份；或許未來對微生物以及深海生物有更多的了解後，我們會找到更多不一樣的氨基酸，也或許標準蛋白質氨基酸的名單會變得更長也不一定喔！

參考資料：

Wikipedia. Pyrrolysine.

Srinivasan, G; James, C. M.; Krzycki, J. A. 2002. Pyrrolysine encoded by UAG in Archaea: charging of a UAG-decoding specialized tRNA. Science. 296 (5572): 1459–1462. doi:10.1126/science.1069588