酵素法合成右旋之胺基酸與多肽

Enzymatic synthesis of D-amino acids and their oligomers

戴達夫(Dar-Fu Tai) ； 葉艾璿(Ai-Xuan Yeh)

《化學》 64卷3期 (2006/09) Pp. 377-386

https://doi.org/10.6623/chem.2006029

摘要

一些以酵素催化生產右旋胺基酸和含右旋胺基酸胜肽已被發展出來。目前具光學純度之右旋胺基酸的工業上生產方法，乃是使用對右旋胺基酸或左旋胺基酸專一的酵素，將醯化之消旋胺基酸、消旋胺基酸醯胺，進行生物轉化。類似的，右旋胺基酸也可由對應之左旋胺基酸產生，先轉變其為消旋胺基酸，然後將消旋的混合物選擇性的轉化，經由於連續的酵素催化反應，高效的生產右旋胺基酸。右旋胺基酸已經被發現在多種自然的胜肽中。這些包括鴉片胜肽和抗菌胜肽、神經胜肽、荷爾蒙等。應用部分或者全部由右旋胺基酸組合的胜肽已重新的引發熱潮。這些胜肽比自然之胜肽更加穩定於蛋白酵素之水解，而且他們有潛能成為經由合成產生之具生物活性的成份。天然的酵素如右旋胺基胜肽酵素、右旋胺基酸醯胺酵素、右旋胺基酸醯化酵素、右旋乙内醯酵素、蛋白水解酵素或脂肪水解酵素，能被應用來製造右旋胺基酸，或在適當的反應條件下促進逆反應，來合成右旋胺基酸多肽。最後，依據右旋胺基酸之衍生物是否能成為基質以及其被水解的速率，衡量其是否為各別酵素所能接受的醯基提供者、與親核基，這些資訊方便吾等歸納設計出有效率之右旋胜肽的合成。

關鍵字

右旋胺基酸 ； 酵素合成法 ； 含右旋胺基酸之胜肽 ； 胜肽合成

並列摘要

Several enzymatic methods for the production of D-amino acids and oligopeptides containing D-amino acids have been developed. Nowadays, optically pure D-amino acids are industrially manufactured by biotransformation of acyl-DL-amino acids, DL-amino acid amides, with a D-isomer or L-isomer specific enzyme. Similarly, D-amino acids have been produced from their corresponding L-isomer, which is transformed to the DL-form. Then the racemic mixture is selectively converted. As a result of successive enzymatic reactions, D-amino acids can be efficiently produced. D-Amino acids have been detected in a variety of natural peptide. These include opiate and antimicrobial peptides, neuropeptides, and hormones. There has been a regain of interest in the applications of peptides assembled partly or totally from D-amino acids. Such peptides are much more stable to proteolysis than natural L-peptides and they have considerable potential as synthetic biologically-active components. Enzymes from nature, such as D-aminopeptidase, D-amino acid amidase, alkaline D-peptidase, D-aminoacylase, proteases, or lipase, either offer potential application in the production of D-amino acids, or the synthesis of their oligomers by promoting the reversed reaction under appropriate conditions. Finally, according to their ability to perform as a substrate and the rate of hydrolysis, D-amino acid derivatives were also evaluated as the specific acyl donor and nucleophile to the individual enzyme. This information facilitates us to design and synthesize D-peptides efficiently.

並列關鍵字

D-amino acids ； enzymatic synthesis ； peptides containing D-amino acids ； peptide synthesis