〔時報資訊〕更新日期： 2007/04/03 09:44 記者：【閻紀宇／綜合二日外電報導】
病患輸血時，血型是否匹配是攸關性命的大事，O 型血液可以輸給任何血型的人，但各國血庫也因此長期有O 型血液存量偏低的困擾。科學家研發出將 A 型、B 型與 AB 型血液轉化為 O 型血液的方法，未來可望徹底解決血型匹配與血庫血荒的問題。
圖1. A general view of the molecular structure of Elizabethkingia meningosepticum N-acetylgalactosaminidase in complex with the NAD+ cofactor (in yellow) and the A antigen on the surface of A type red blood cells. The N-acetylgalactosamine molecule recognized and hydrolyzed by the enzyme appears in red. (Credit: Copyright AFMB - CNRS 2007)
目前人們常聽到的 ABO 血型是在 1900 年由奧地利科學家 Karl Landsteiner 所提出。
圖2. 發現 ABO 血型的奧地利科學家 Karl Landsteiner（圖片來源：http://osulibrary.oregonstate.edu/specialcollections/coll/pauling/blood/people/landsteiner.html）
人類的血型決定於紅血球表面醣類抗原的型態，具 A1 或 A2 抗原者為 A 型，具 B 抗原者為 B 型，兼具者為AB 型，全無者為 O 型，除了 O 型血液可以輸給各型之外（所以 O 型血稱為 universal donor），其他三型血液都只能輸給同血型者，否則將引發足以致命的副作用。美國醫界估計，每一萬兩千次輸血中，會發生一次血型比對錯誤。
圖3. ABO 血球表面抗原狀態
（圖片來源：http://learn.genetics.utah.edu/units/basics/blood/types.cfm）
丹麥哥本哈根大學克 勞森 教授領導的團隊，從兩千五百多種細菌與真菌中找到兩種細菌，它們會分泌兩種去醣基酵素（glycosidase enzyme），可去除 A 型、B 型與 AB 型血液的紅血球表面醣類抗原，變成「酵素轉化 O 型」（ECO）血液。
圖4. Structural basis of the ABO blood group antigens.（圖片來源：Nature Biotechnology, 25, 454 - 464 (2007)）
其實，早在 1980 年代，科學家就發現咖啡豆含有一種酵素，可去除 B 型血液紅血球的 B 型抗原，不過只適用於 B 型血液，而且效率相當低。克勞森表示，新發現的 B 型抗原去醣基酵素效率是前者的一千倍，而且可在 pH 值中性的環境中工作。
圖5. Crystals of Elizabethkingia meningosepticum N-acetylgalactosaminidase used to solve the molecular structure by X-ray crystallography.
克勞森的團隊與美國麻州的 ZymeQuest 公司合作，已研發出製造 ECO 血液的機器，可在九十分鐘內處理八個單位的血液（一單位是 250 CC）；所製造的 ECO 血液已進入第二階段人體臨床試驗，如果一切順利，新機器可望於 2011 年率先在歐洲上市，美國要再多等幾年。
Group O Blood For Everyone?
Science Daily — Two families of enzymes that could remove the blood group A, B and AB antigens from the surface of red blood cells have just been identified by the Architecture and Function of Biological Macromolecules Laboratory (CNRS – Université Aix-Marseille 1 and 2), in collaboration with ZymeQuest Inc. These two families of enzymes have unique properties and are so efficient that large scale conversion of blood groups A, B and AB into universal donor group O is feasible.
圖6. Overall structure of the E. meningosepticum a-N-acetylgalactosaminidase.
The ABO system was discovered by Karl Landsteiner in 1900. Blood group O is known as the universal donor because it can be transfused to all blood groups (A, B, AB and O). But transfusing group A blood to a group B patient (and vice versa) causes an ABOaccident and can be lethal. Labeling errors still cause deaths each year.
Conversion of blood groups A, B and AB into group O, universal donor, would avoid these risks. But above and beyond that, and more significantly, converting blood groups would also have a great economic advantage, because at present, transfusion centers have to carry and constantly renew stocks of 4 types of blood (A, B, AB and O). The difficulty entailed in carrying sufficient stocks of certain blood groups is well known, for example in the case of seasonal variation or a sudden increase in demand following a disaster. So the possibility of converting blood groups would solve these problems by making a significant improvement in the supply of group O.
The new enzymes, discovered after detailed exploration of the great diversity of known bacteria available, come from bacteria with sometimes unlikely names such as Elizabethkingia, (Queen Elizabeth). These enzymes can remove the galactose or N-acetylgalactosamine molecules present on the surface of the red blood cells characterizing the A, B and AB antigens. The prohibitive cost and low efficiency of previously known enzymes meant that using them for blood group conversion was not viable. But these new enzymes have an unusual catalytic mechanism that changes that.
The Architecture and Function of Biological Macromolecules Laboratory uses X-ray crystallography to study the 3-D structures of the enzymes and classify them according to their amino acid sequence. This database, known as CAZy (Carbohydrate-Active Enzymes), has many applications worldwide including discovering genes in the genome structure. Researchers use structural data to identify the architecture of active sites and understand their mechanism of action. The aim is to create tools which, in this case, improve enzyme efficiency.
Reference: Bacterial glycosidases for the production of universal red blood cells, Qiyong P Liu, Gerlind Sulzenbacher, Huaiping Yuan, Eric P Bennett, Greg Pietz, Kristen Saunders, Jean Spence, Ed Nudelman, Steven B. Levery, Thayer White, John M. Neveu, Williams Lane, Yves Bourne, Martin L Olsson, Bernard Henrissat, Henrik Clausen, Nature Biotechnology, April 2007, 25, 454-464.
Note: This story has been adapted from a news release issued by CNRS.
原始論文摘要：
http://www.nature.com/nbt/journal/v25/n4/abs/nbt1298.html