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       ÀÌÁ¤°É ±³¼ö        2014.03.04 13:48        21830
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  °Ç±¹´ëÇб³ ÀÌÁ¤°É

 

1. °³¿ä
È¿¼Ò´Â Àü ¼¼°èÀûÀ¸·Î ´ë´ëÀûÀÎ ¿¬±¸°³¹ß ¹× »ê¾÷È­°¡ ÃßÁøµÇ°í ÀÖ´Â White Biotechnology ºÐ¾ßÀÇ ÇÙ½ÉÀ¸·Î ºÎ°¢µÇ¾úÀ¸¸ç, ±×·ÎÀÎÇØ ¼¼°èÀû È­ÇÐ ¹× Á¦¾à, »ý¸í°øÇÐ ±â¾÷µéÀÌ °¢°¢ÀÇ ¸ñÀû¿¡ ¸Â´Â È¿¼ÒÀÇ °³¹ß¿¡ ÁýÁßÀûÀ¸·Î ÅõÀÚÇÏ°í ÀÖÀ¸¸ç, ±× ½ÃÀåÀº ±Þ¼Óµµ·Î ÆØâÇÏ°í ÀÖ´Ù (Fig. 1).

                  

  Fig. 1. »ê¾÷¿ë È¿¼Ò ½ÃÀåÀÇ ÇöȲ. Animal feed, starch processing, detergent, textile, biofuel µî µî ´Ù¾çÇÑ ºÐ¾ß¿¡¼­ »ê¾÷¿ë È¿¼Ò°¡ »ç¿ëµÇ°í ÀÖÀ¸¸ç, ´ë±Ô¸ð ½ÃÀåÀ» Çü¼ºÇÏ°í ÀÖÀ½ (Cherry and Fidantsef 2003, Walsh 2006).

 

°ú°Å¿¡´Â ÀÚ¿¬°è¿¡ Á¸ÀçÇÏ°í ÀÖ´Â ´Ù¾çÇÑ ¹Ì»ý¹°µéÀÌ È¿¼ÒÀÇ ´Ù¾ç¼ºÀ» È®º¸ÇÏ´Â Áß¿äÇÑ ÀÚ¿øÀ̾ú´Ù. Áï, ¸ñÀû¿¡ ¸Â°Ô È¿¼Ò¸¦ ¼³°èÇϱ⺸´Ù´Â ¸ñÀû¿¡ ºÎÇյǴ ȿ¼Ò¸¦ ¹æ´ëÇÑ »ýÅ°迡¼­ Ž»öÇÏ´Â bioprospectingÀÌ ÁÖµÈ È¿¼Ò ¹ß°ß ¹æ¹ýÀ̾ú´Ù. ±×·¯³ª, ÀÚ¿¬°è¿¡¼­ ¹ß±¼ÇÑ À¯ÀüÀÚ¿øÀ» ½ÇÁ¦ »ê¾÷ ÇöÀå¿¡ ¹Ù·Î ÀÌ¿ëÇϱ⿡´Â ¿©·¯ °¡Áö Á¦¾àÀÌ µû¸¥´Ù. Áï, ºÐ¸®ÇÑ È¿¼ÒÀÇ ºñÈ°¼º, pH ¹× ¿­ ¾ÈÁ¤¼º, ±âÁúƯÀ̼º, ¸®°£µå¿ÍÀÇ Ä£È­¼º µîÀÌ ½ÇÁ¦ ÀǾà¿ëÀ̳ª »ê¾÷ÀûÀ¸·Î »ç¿ëÇϱ⿡´Â ¸¹Àº ÇÑ°èÁ¡À» ³ªÅ¸³½´Ù. 1990³â´ëºÎÅÍ À̸¦ ÇØ°áÇϱâ À§ÇØ ¸ñÀû¿¡ ¸Â´Â Ư¼ºÀ̳ª »õ·Î¿î ±â´ÉÀ» Áö´Ñ ´Ü¹éÁúÀ» ¼³°èÇÏ´Â ¹æÇâÀ¸·Î paradigm shift°¡ ÀϾ È¿¼Ò È°¼º, ¾ÈÁ¤¼º, ±âÁú ƯÀ̼º µîÀ» ¿øÇÏ´Â ¹æÇâÀ¸·Î ¼³°èÇÏ¿© ¸ÂÃãÇü È¿¼Ò¸¦ Á¦ÀÛÇÏ´Â ´Ü¹éÁú°øÇп¡ ÀÇÇØ ÁÖ·Î ¿¬±¸°¡ ÁøÇàµÇ°í ÀÖ´Ù. °íÀüÀû È¿¼Ò ¼³°è·Î´Â ´Ü¹éÁú ¼öÁØ¿¡¼­ chemical¿¡ ÀÇÇØ Æ¯Á¤ ¾Æ¹Ì³ë»ê Àܱ⸦ º¯ÇüÇÏ´Â È­ÇÐÀû º¯Çü¹ýÀÎ atom replacement, segment reassembly µîÀÌ »ç¿ëµÇ¾ú´Ù. ±×·¯³­ ´ÜÁö ¸î¸î Àܱ⸸ chemical¿¡ ÀÇÇØ º¯ÇüµÉ ¼ö ÀÖ°í, ±â¹ý ÀÚü°¡ º¹ÀâÇÏ°í, time-consuming ÇÏ¿© ³Î¸® »ç¿ëµÇÁö ¸øÇÏ¿´´Ù. 2000³â´ë ÀÌÈÄ·Î À¯ÀüÀÚ °ü·Ã ±â¼ú ¹× ±¸Á¶»ý¹°ÇÐÀÌ ±Þ¼ÓÈ÷ ¹ß´ÞÇϸ鼭 À¯¿ëÇÑ »õ·Î¿î »ýü ºÐÀÚ¸¦ ¸¸µé±â À§ÇÑ ¸¹Àº Á¢±Ù ¹æ¹ýÀÌ °³¹ßµÇ¾ú´Ù. ÀÌ Á¢±Ù ¹æ¹ýµéÀº Å©°Ô 3°¡Áö·Î ºÐ·ùµÉ ¼ö ÀÖ´Ù: directed evolution, rational design ¹× semi-rational design ¶Ç´Â designed evolution°ú °°Àº ÇÏÀ̺긮µå ½Ã½ºÅÛ. ÀÌµé ±â¹ýÀ» ÅëÇØ ÀÚ¿¬°è¿¡ Á¸ÀçÇÏÁö ¾Ê¾Ò´ø ¿ì¼öÇÑ Ã˸ŵéÀÌ Á¦À۵ǾúÀ¸¸ç, º» º¸°í¿¡¼­´Â ´Ü¹éÁú °øÇÐÀ» À§ÇÑ À̵é ÁøÈ­Àû Á¢±Ù ¹æ¹ýµéÀÇ »õ·Î¿î µ¿Çâ°ú ¸î¸î Èï¹Ì·Î¿î ÀÀ¿ë¿¡ ´ëÇؼ­ ³íÀÇÇÑ´Ù.

 

2. ´Ü¹éÁú °øÇÐ ¿¬±¸ ±â¹ý ¹× µ¿Çâ
È¿¼ÒµéÀº ¸Å¿ì ´ÙÀç´Ù´ÉÇÏ°í ´É¼÷ÇÑ Ã˸ÅÀÌ´Ù. ¼ö¹é¸¸ ³â µ¿¾ÈÀÇ ´ÙÀ© ÁøÈ­¿¡ ÀÇÇØ ÃÖÀûÈ­µÈ À̵éÀº È­ÇÐ ¹ÝÀÀÀ» Å©°Ô °¡¼Ó½Ãų ¼ö ÀÖ°í ³ôÀº ±âÁú ƯÀ̼º»Ó ¾Æ´Ï¶ó Á¤±³ÇÑ °Å¿ï»ó ¼±Åüº°ú ÀÔü ¼±ÅüºÀ» È®º¸ÇÒ ¼ö ÀÖ´Ù. ÀÌ·¯ÇÑ ¼º´É Ư¼ºµéÀÌ »ýü Ã˸Ÿ¦ ½ÇÇè½Ç ¹× »ó¾÷ °øÁ¤¿¡¼­ ºñ´ëĪÀû ÇÕ¼ºÀ» À§ÇÑ ¸Å·ÂÀûÀÎ È帷Π¸¸µç´Ù. ±×·¯³ª ÀÚ¿¬¿¡¼­ÀÇ È¿¼ÒÀÇ ±â´É°ú °úÇÐÀÚµé ¹× ±â¼úÀÚµéÀÌ »ý°¢ÇÏ´Â »ýü ¿Ü ¿ëµµ¸¦ À§ÇÑ ±¸Ã¼Àû ¿ä°Çµé »çÀÌ¿¡ Á¾Á¾ À¯ÀÇÇÑ Â÷ÀÌ°¡ ÀÖ´Ù. ÀÌ·¯ÇÑ Â÷ÀÌÀÇ ±Øº¹À» À§ÇØ ´ÙÀ½°ú °°Àº È¿¼Ò Á¶ÀÛÀÌ Ç¥Àû ´Ü¹éÁúÀÇ Ã˸ŠƯ¼º, »ý¹° ¹°¸®ÇÐÀû ¹× ºÐÀÚ ÀÎ½Ä Æ¯¼ºÀÇ Á¶ÀýÀ» À§ÇØ ¼±ÅõǴ Àü·«ÀÌ µÇ°í ÀÖ´Ù.

 

1) Directed evolution
Directed evolutionÀº ±¸Á¶¿¡ ´ëÇÑ ±íÀÌ ÀÖ´Â ÀÌÇØ ¾øÀÌ ÃÊ°í¼Ó ½ºÅ©¸®´× ½Ã½ºÅÛ¿¡ ±â¹ÝÇÏ¿© ºñ±³Àû ºü¸£°Ô È¿¼Ò¸¦ °³·®ÇÒ ¼ö ÀÖ°Ô ÇÑ´Ù. Directed evolutionÀº ´ëÇ¥ÀûÀ¸·Î µÎ °¡Áö Á¢±Ù ¹æ¹ý¿¡ ÀÇÇØ ÁøÇàµÈ´Ù; i. °ü·ÃµÈ ¼­¿­ÀÇ Á¶ÇÕÀ» ¹«ÀÛÀ§·Î ÀçÁ¶ÇÕ (¿¹. À¯ÀüÀÚ shuffling), ii. ´ÜÀÏÇÑ ´Ü¹éÁú ¼­¿­¿¡ ¹«ÀÛÀ§ÀÇ º¯È­ µµÀÔ (¿¹. error prone PCR). ÀÌ·¯ÇÑ directed evolutionÀÇ ÀåÁ¡Àº ±¸Á¶ Á¤º¸°¡ ÇÊ¿ä ¾øÀ¸¸ç È°¼º ºÎÀ§¿¡¼­ ¸Õ ¿¹»óÄ¡ ¾ÊÀº À§Ä¡¿¡¼­ÀÇ º¯ÀÌ°¡ µµÀ﵃ ¼ö ÀÖ´Ù´Â °ÍÀÌ´Ù. Áï, Directed evolutionÀº ½ÇÇè½Ç ¼öÁØ¿¡¼­ ÀÚ¿¬ ÁøÈ­ °úÁ¤À» ¸ð»çÇÏ´Â ±â¹ýÀ¸·Î ¹Ýº¹ÀûÀÎ ´Ü¹éÁú º¯ÀÌü library ±¸Ãà°ú ÃÊ°í¼Ó ½ºÅ©¸®´×¹ý¿¡ ÀÇÇÑ ¸ñÀû ´Ü¹éÁúÀÇ  ½ºÅ©¸®´×/selectionÀ¸·Î ±¸¼ºµÇ¾î ÀÖ´Ù. ¶ÇÇÑ ¸ñÀû È¿¼ÒÀÇ ±¸Á¶ ¹× ±â´É¿¡ ´ëÇÑ ÀÚ¼¼ÇÑ Á¤º¸¸¦ ¿ä±¸ÇÏÁö ¾ÊÀ½¿¡µµ ºÒ±¸ÇÏ°í, È®º¸µÈ º¯ÀÌüÀÇ ±Ô¸íÀ» ÅëÇØ ´Ü¹éÁú ±¸Á¶¿Í ±â´É¿¡ ´ëÇÑ Á¤º¸¸¦ ¾òÀ» ¼ö ÀÖ´Â top-down approach¿¡ ÇØ´çÇÑ´Ù.  ±×·¯³ª ÇÑ Â÷·ÊÀÇ µ¹¿¬º¯ÀÌ ¹× ½ºÅ©¸®´×¿¡ ÀÇÇØ È®º¸µÇ´Â º¯È­´Â ´ë°³ ±× È¿°ú°¡ ÀÛ´Ù. ±×·ÎÀÎÇØ ¼öÂ÷·ÊÀÇ Ãß°¡ÀûÀÎ ÁøÈ­°¡ Àû¿ëµÇ¾î¾ß Çϸç, ¸¹Àº ¼öÀÇ º¯Á¾ÀÌ ¼±º°µÇ¾î¾ß ÇϹǷΠ¸¹Àº ½Ã°£°ú ³ëµ¿·ÂÀÇ ¼Ò¸ð¸¦ ¿ä±¸ÇÏ´Â °æ¿ì°¡ ´ëºÎºÐÀÌ´Ù. ±×¿Í ´õºÒ¾î ½Å·Ú¼ºÀÌ ³ô°í ´ë¿ë·® 󸮰¡ °¡´ÉÇÑ ÃÊ°í¼Ó ºÐ¼®¹ýÀ» ÇʼöÀûÀ¸·Î ¿ä±¸ÇÑ´Ù. ¶ÇÇÑ ´Ü¼øÇÑ È¿¼ÒÀÇ ±â´É °³¼± ¸ñÀûÀÌ ¾Æ´Ï¶ó ½Å±Ô ±âÁúƯÀ̼º, ÃÊ°íÈ°¼º µî°ú °°Àº »õ·Î¿î ±â´ÉÀ» °®´Â È¿¼Ò¸¦ ¾ò±â À§Çؼ­´Â ´ÙÁß µ¹¿¬º¯À̸¦ ¿ä±¸Çϴµ¥, Çö ±â¼ú·Î´Â ´ÙÁß µ¹¿¬º¯ÀÌ°¡ µµÀÔµÈ °³Ã¼ÀÇ ½ºÅ©¸®´×ÀÌ ¿ëÀÌÇÏÁö ¾Ê´Ù´Â ¹®Á¦Á¡ÀÌ ÀÖ´Ù. Áï, Fig. 2¿Í °°ÀÌ quadruple mutant¸¸ µÇ´õ¶óµµ ÇöÀçÀÇ ±â¼ú·Î´Â ÇÊ¿äÇÑ libraryÀÇ ±Ô¸ð¸¦ È®º¸ÇÒ ¼ö ¾ø±â ¶§¹®¿¡ Á¤»óÀûÀÎ ½ºÅ©¸®´×ÀÌ ºÒ°¡´ÉÇÏ´Ù.  
    

Fig. 2. Limitation of directed evolution. ´ÙÁß µ¹¿¬º¯À̸¦ ½ºÅ©¸®´× Çϱ⿡´Â ¶óÀ̺귯¸® ±Ô¸ð¿¡ ÇÑ°è°¡ ÀÖÀ¸¸ç, ±×·ÎÀÎÇØ ½Å±â´ÉÀ» °®´Â È¿¼ÒÀÇ Å½»öÀÌ ¸Å¿ì ¾î·Á¿ò.

 

2) Rational design
´Ü¹éÁú ±â´ÉÀº º¸Åë 3Â÷¿ø ±¸Á¶¿Í ±ä¹ÐÇÏ°Ô ¿¬°èµÇ¾î¼­ °íºÐÀÚ¿¡¼­ÀÇ Çϳª ¶Ç´Â ±× ÀÌ»óÀÇ ¾Æ¹Ì³ë»êÀÇ Ä¡È¯À» ´ÜÁö ¼­¿­ ¸Æ¶ô¿¡¼­ÀÇ ÇÔ¼ö¸¸ÀÌ ¾Æ´Ñ ±¸Á¶Àû À§»ó°ü°è¿¡¼­ÀÇ ÇÔ¼ö·Îµµ ¸¸µç´Ù. PDB ´Ü¹éÁú ±¸Á¶ ¼ýÀÚ Áõ°¡¿Í »óµ¿°ü°è ¸ðµ¨¸µÀÇ Áøº¸´Â ´Ü¹éÁú °øÇÐÀÚµéÀÌ È°¼º ºÎÀ§¿Í ¿µ¿ª ÀÎÅÍÆäÀ̽º ¶Ç´Â °æø ¿µ¿ª¿¡ °¡±î¿î ÇÙ½É Àܱ⸦ º¸´Ù È¿°úÀûÀ¸·Î ã¾Æ³»´Âµ¥ °¡Ä¡ ÀÖ´Â µµ¿òÀ» Á¦°øÇÏ¿© ¶Ù¾î³­ ¶óÀ̺귯¸® ¼³°è¸¦ °¡´ÉÇÏ°Ô ÇÑ´Ù. Rational design¿¡¼­´Â »ýÈ­ÇÐÀû ÀÚ·á ¹× ´Ü¹éÁú ±¸Á¶ ÀÚ·á¿¡ ±Ù°ÅÇÏ¿© ´Ü¹éÁú Ư¼º °³·®¿¡ ÇÊ¿äÇÑ µ¹¿¬º¯ÀÌ À§Ä¡¸¦ Á¦¾ÈÇÏ¸ç µ¹¿¬º¯ÀÌ´Â À§Ä¡ ƯÀ̼º µ¹¿¬º¯ÀÌ À¯¹ß¿¡ ÀÇÇØ µµÀԵȴÙ. Rational design Á¢±Ù ¹æ¹ýÀÇ ÀåÁ¡µé Áß Çϳª´Â À¯ÀÍÇÑ µ¹¿¬º¯ÀÌÀÇ °¡´É¼ºÀÌ Áõ°¡µÇ°í ¶óÀ̺귯¸® Å©±â°¡ À¯ÀÇÇÏ°Ô °¨¼ÒµÇ¹Ç·Î ¶óÀ̺귯¸®ÀÇ ¼±º°¿¡ ´õ ÀûÀº ³ë·Â°ú ½Ã°£ÀÌ ¾²Àδٴ °ÍÀÌ´Ù. ÀÌ°ÍÀº 󸮷®ÀÌ Å« ºÐ¼®¹ýÀ» ÀÌ¿ëÇÒ ¼ö ÀÖÀ» °æ¿ì¿¡ ƯÈ÷ À¯¸®ÇÏ´Ù. ÃÖ±Ù rational design¿¡ ¸¹ÀÌ Àû¿ëµÇ°í ÀÖ´Â computational ´Ü¹éÁú ¼³°èÀÇ ºÐ¾ß´Â µÎ °¡Áö ¸ñÇ¥¸¦ Ãß±¸ÇÑ´Ù. Çϳª´Â ½ÇÁ¦ÀûÀÎ °ÍÀ¸·Î ¸ñÀû ±â´ÉÀÌ °­È­µÈ ´Ü¹éÁú »ê¹°À» È®º¸ÇÏ´Â °ÍÀÌ°í, µÎ ¹ø° ¸ñÇ¥´Â °øÇÐÀû ¸ñÇ¥º¸´Ù´Â °úÇÐÀû ¸ñÇ¥·Î¼­, ´Ü¹éÁúÀÇ Æ¯¼º¿¡ ¿µÇâÀ» ¹ÌÄ¡´Â ¿ø¸®¿¡ ´ëÇÑ Á¤·®Àû ¼³¸íÀ» Ãß±¸ÇÏ´Â °ÍÀÌ´Ù. ÀÌ¿Í °°ÀÌ rational designÀº ´Ü¹éÁúÀÇ ±¸Á¶Á¤º¸¿¡ ±Ù°ÅÇÏ¿© ¸ñÀû ´Ü¹éÁúÀÇ Æ¯Á¤ À§Ä¡¿¡ rational alterationÀ» °¡ÇÏ¿© ´Ü¹éÁúÀÇ ±â´É¿¡ ¿øÇÏ´Â º¯È­¸¦ Ãß±¸ÇÏ´Â ¹æ¹ýÀÌ´Ù. µû¶ó¼­ ÀÌ ¹æ¹ýÀº È¿¼Ò ±¸Á¶, ±â´É, Ã˸Š±âÀÛ µî ÀÇ ÀÚ¼¼ÇÑ Á¤º¸¸¦ ¿ä±¸ÇÏ´Â bottom-up approach¿¡ ÇØ´çÇÏ´Â ±â¹ýÀÌ´Ù. ±×·¯³ª ±¸Á¶»ý¹°ÇÐ ±â¹ýÀÌ ºñ±³Àû ÃÖ±Ù¿¡ º¸ÆíÈ­µÇ¾úÀ¸¸ç, ±×·ÎÀÎÇØ ´Ù¾çÇÑ È¿¼ÒÀÇ ±¸Á¶°¡ ÃæºÐÈ÷ ¹àÇôÁ® ÀÖÁö ¾Ê±â ¶§¹®¿¡ ±¸Á¶¿¡ ±Ù°ÅÇÑ ´Ü¹éÁú°øÇÐ ¿¬±¸, Áï rational design¿¡ ÀÇÇÑ ¿¬±¸°¡ ¸ðµç È¿¼Ò¸¦ ´ë»óÀ¸·Î ü°èÀûÀ¸·Î ¼öÇàµÇ´Â µ¥ ÇÑ°è°¡ ÀÖ´Ù.
 
3) Semi-rational design ¶Ç´Â designed evolution
Semi-rational designÀº ÇÕ¸®Àû ¹× ¹«ÀÛÀ§ ´Ü¹éÁú ¼³°èÀÇ ÀåÁ¡µéÀ» °áÇÕÇÏ¿© »ýÈ­ÇÐÀû, ±×¸®°í/¶Ç´Â ±¸Á¶Àû ÀÚ·á¿¡¼­ µµÃâµÈ Áö½Ä¿¡ ±Ù°ÅÇÏ¿© ´õ ÀÛ°í ½º¸¶Æ®ÇÑ ¶óÀ̺귯¸®¸¦ »ý¼ºÇÑ´Ù (Lutz S and Bornscheuer U, 2009). ÇÑ ¿¹´Â ±¸Á¶Àû ÀÚ·á¿¡¼­ µµÃâµÈ Á¤º¸¸¦ »ç¿ëÇÏ¿© °ü½É ºÎÀ§(¿¹, È°¼º ºÎÀ§)¿¡ ÀÖ´Â ¾Æ¹Ì³ë»êµéÀ» È®ÀÎÇÏ°í ±× ¾Æ¹Ì³ë»êµéÀÌ ¹«ÀÛÀ§·Î ¶Ç´Â ºÎÀ§ Æ÷È­ µ¹¿¬º¯ÀÌ À¯¹ß¿¡ ÀÇÇؼ­ Çϳª¾¿ ¶Ç´Â ÇÔ²² µ¹¿¬º¯ÀÌ°¡ µÇ´Â CASTing (combinatorial active site saturation test)ÀÌ´Ù. Ç¥Àû À§Ä¡¿¡¼­ µ¹¿¬º¯ÀÌÀÇ ¹«ÀÛÀ§ Á¶ÇÕ ¶Ç´Â »ó°ü µ¹¿¬º¯ÀÌ´Â ´ÜÀÏ ºÎÀ§¿¡ ƯÀÌÀûÀÎ µ¹¿¬º¯ÀÌ À¯¹ß¿¡¼­ ´©¶ôµÇ¾úÀ» ¼ö ÀÖ´Â ½Ã³ÊÁö È¿°ú¸¦ °¡Á®¿Ã ¼ö ÀÖ´Ù. ±×·¯³ª, ÀÌ Á¶ÇÕÀû Á¢±Ù ¹æ¹ýµéÀº ¶óÀ̺귯¸® Å©±â¸¦ Å©°Ô Áõ°¡½ÃÅ°¹Ç·Î ÃÖ±Ù ¸î ³â°£ °¡»ó ¶óÀ̺귯¸®¸¦ °Ë»çÇÏ¿© ´Ü¹éÁú ÁÖ¸§¿¡ ºÒ¸®ÇÒ °ÍÀ¸·Î ¿¹»óµÇ´Â µ¹¿¬º¯À̸¦ ¹èÁ¦ÇÔÀ¸·Î½á ¶óÀ̺귯¸® Å©±â¸¦ ÁÙÀ̵µ·Ï µ½´Â ¿©·¯ °¡Áö computational ¹æ¹ýµéÀÌ °³¹ßµÇ¾ú´Ù. ´ÙÀ½Àº ±Ù·¡ »ç¿ëµÇ°í ÀÖ´Â ´Ù¾çÇÑ semi-rational design ¶Ç´Â designed evolution ±â¹ýÀ» ¼Ò°³ÇÑ´Ù.

 

- ¼­¿­±â¹Ý È¿¼Ò Àç¼³°è
´Ü¹éÁú ¼­¿­ space¿¡¼­ ±â´É¼ºÀÇ ¡®islands¡¯¸¦ º¸´Ù È¿°úÀûÀ¸·Î ã°í È®ÀÎÇÏ´Â ÈçÇÑ Àü·«Àº ÁøÈ­ Á¤º¸¸¦ »ç¿ëÇÏ´Â °ÍÀ̾ú´Ù. ´ÙÁß ¼­¿­ Á¤·Ä (MSAs) ¹× °èÅë ¹ß»ý ºÐ¼®ÀÌ ¾Æ¹Ì³ë»ê º¸Á¸°ú »óµ¿ ´Ü¹éÁú ¼­¿­ ¹× ±¸Á¶ Áý´Üµé °£ Á¶»óÀÇ °ü°è¸¦ Ž»öÇϴ ǥÁØ µµ±¸°¡ µÇ¾ú´Ù. ÀÌ Åë°è°¡ Å« ÀÚ¿¬ ¼­¿­ Ç®¿¡¼­ µµÃâµÇ¾úµç ½ÇÇè½Ç¿¡¼­ Áß¼º È帧 ½ÇÇèÀ» ÅëÇؼ­ µµÃâµÇ¾úµç, ÀÌ ÀÚ·á´Â ±â´ÉÀû ÇÖ ½ºÆÌÀ» È®ÀÎÇÏ°í ±¹¼Ò ¾Æ¹Ì³ë»ê º¯µ¿¼º Æò°¡ ¹× ÇÕÀÇ ¼³°è¸¦ À§ÇØ ´Ü¹éÁú °øÇÐÀÚ¿¡°Ô Áß¿äÇÏ´Ù. ÀÌ ¸ñÀûÀ» À§ÇÑ ¸¹Àº ¼öÀÇ ÀÚ·á ºÐ¼® ¼ÒÇÁÆ®¿þ¾î Áß¿¡¼­ (Damborsky J and Brezovsky J 2009, Pei J 2008), 2°¡ÁöÀÇ »õ·Î¿î ±â¹Ý Àü»ê µµ±¸°¡ ÁÖ¸ñÇÒ ¸¸ÇÏ´Ù. Áï, HotSpot Wizard ¼­¹ö (
http://loschmidt.chemi.muni.cz/hotspotwizard)´Â ±¤¹üÀ§ÇÑ ¼­¿­ ¹× ±¸Á¶ µ¥ÀÌÅͺ£À̽º °Ë»ö¿¡¼­ ¾òÀº Á¤º¸¸¦ ±â´ÉÀû ÀÚ·á¿Í °áÇÕÇÏ¿© Ç¥Àû ´Ü¹éÁú¿¡ ´ëÇÑ µ¹¿¬º¯ÀÌ ¼º ¸ÊÀ» »ý¼ºÇÑ´Ù (Pavelka A 2009). ÀÌ ½Ã½ºÅÛÀÇ ¼º´ÉÀÌ Rhodococcus rhodochrous·ÎºÎÅÍ À¯·¡ÇÑ haloalkane dehalogenase (DhaA) Á¦ÀÛÀÇ ÀϺηΠÁ¦½ÃµÇ¾ú´Ù (Pavlova et al. 2009). ÀÌ ÀÚ·áµéÀº »ó°ü µ¹¿¬º¯ÀÌ ¹× º¸Á¸°ú °°Àº ÁøÈ­ Ư¡¿¡ ´ëÇÑ ÀÏ·ÃÀÇ ³»ÀåµÈ ÇÊÅ͸¦ ÅëÇÏ¿© È¿°úÀûÀ¸·Î °Ë»öµÉ ¼ö ÀÖ´Ù. ÀÌ µ¥ÀÌÅͺ£À̽ºÀÇ ´Ü¹éÁú °øÇп¡ ´ëÇÑ ÀáÀçÀûÀÎ ÆíÀÍÀÌ È°¼ºµµ ¹× ±âÁú ƯÀ̼ºÀÇ º¯È­»Ó ¾Æ´Ï¶ó (Kuipers et al. 2009, Joosten et al. 2008), °Å¿ï»ó ¼±ÅüºÀÇ °³¼± (Jochens et al. 2010)À» À§ÇÑ ¸ðµ¨ È¿¼Ò¸¦ Ž»çÇÏ´Â 3°ÇÀÇ ¿¬±¸¿¡¼­ Á¦½ÃµÇ¾ú´Ù. ¼­¿­±â¹Ý Á¤º¸¿Í Àü»ê ¸ðµ¨¸µ µµ±¸ÀÇ °áÇÕÀ» ÅëÇؼ­ È¿¼Ò Àç¼³°èÀÇ Ãß°¡ÀûÀÎ ¹ßÀüÀÌ °¡´ÉÇÏ´Ù. ¹«ÀÛÀ§ µ¹¿¬º¯ÀÌ À¯¹ß°ú DNA shuffling ¶óÀ̺귯¸®¿¡¼­ ÀÌÀü¿¡ È®ÀÎµÈ DhaA º¯Á¾¿¡¼­ÀÇ ÁߵÀÇ ±â´ÉÀû °³¼±À» ¼³¸íÇϱâ À§Çؼ­ ºÐÀÚ ¿ªÇÐ ½Ã¹Ä·¹À̼ÇÀ» ¼öÇàÇÏ´Â µµÁß¿¡, Damborsky¿Í ±×ÀÇ µ¿·áµéÀÌ À¯ÀÍÇÑ µ¹¿¬º¯À̵éÀÌ È°¼º ºÎÀ§¿¡ Á÷Á¢ ¿µÇâÀ» ¹ÌÄ¡Áö ¾Ê°í È¿¼ÒÀÇ 2°³ÀÇ Á¢±Ù ÅͳÎÀÇ ¹èÁ º¯È­¸¦ ÅëÇؼ­ Ã˸Š¼º´ÉÀ» °³¼±ÇÑ´Ù´Â °ÍÀ» ¹ß°ßÇß´Ù (Banas et al. 2006). HotWizard¿¡ ÀÇÇØ À¯µµµÈ ƯÁ¤ÇÑ Ä¡È¯ÀÌ À§Ä¡µé Áß 2°³¿¡ µµÀԵǾú°í Çâ»óµÈ dehalogenase È°¼º¿¡ ´ëÇÑ ³ª¸ÓÁö 3°³ ¾Æ¹Ì³ë»ê ÀܱâÀÇ ¿µÇâÀÌ ÀÛÀº ºÎÀ§Æ÷È­ µ¹¿¬º¯ÀÌ À¯¹ß ¶óÀ̺귯¸®¿¡ ÀÇÇؼ­ ½±°Ô Æò°¡µÉ ¼ö ÀÖ¾ú´Ù. ÀÌ Àü·«Àº À¯ÀÇÇÏ°Ô ´õ ³ôÀº È°¼ºÀÌ ÀÖ´Â È¿¼Ò º¯Á¾À» ºÐ¸®Çϴµ¥ À¯¿ëÇÒ »Ó ¾Æ´Ï¶ó °¡Àå À¯ÀÍÇÑ ¾Æ¹Ì³ë»ê ġȯÀ» È®ÀÎÇϴµ¥ ¸Å¿ì Áß¿äÇÑ °ÍÀ¸·Î È®ÀεǾú´Ù.

 

- ±¸Á¶ ±â¹Ý È¿¼Ò Àç¼³°è
È°¼º ºÎÀ§¿¡ °¡±î¿î Àܱ⠻Ӹ¸¾Æ´Ï¶ó ¸Ö¸® ¶³¾îÁø ÀܱâÀÇ µ¹¿¬º¯ÀÌ À¯¹ß¿¡ ±Ù°ÅÇÑ Çõ½ÅÀûÀÎ ±¸Á¶ ±â¹Ý È¿¼Ò Àç¼³°è°¡ ´ÙÀ½°ú °°ÀÌ ¼öÇàµÇ¾ú´Ù. Áï, Reetz ¿Í ±×ÀÇ µ¿·áµéÀº È°¼º ºÎÀ§¿¡ °¡±î¿î ÀܱâÀÇ µ¹¿¬º¯ÀÌ À¯¹ßÀ» ³Ñ¾î¼­ ¼ÒÀ§ À¯µµµÈ ¾Ë·Î½ºÅ׸¯ È¿°ú¸¦ ÅëÇؼ­ ¿øÀ§Ä¡ µ¹¿¬º¯ÀÌÀÇ ÀáÀçÀûÀÎ ±â´ÉÀû ÆíÀÍÀ» Ž±¸Çß´Ù (Wu et al. 2010). À̵éÀº Thermobifida fusca·ÎºÎÅÍ À¯·¡ÇÑ ¿­ ¾ÈÁ¤ÀûÀÎ Bayer-Villiger monooxygenaseÀÇ FAD ¿Í NADP °áÇÕ ¿µ¿ªÀÇ ÀÎÅÍÆäÀ̽º¿¡ ÃÊÁ¡À» µÎ¾ú´Ù (Malito et al. 2004, Fraaije et al. 2005, 66:393-400). ±¸Á¶ ºÐ¼®ÀÌ Æ÷È­ µ¹¿¬º¯ÀÌ°¡ À¯¹ßµÈ 2°³ ¿µ¿ªÀÇ °æø ¿µ¿ª °¡±îÀÌ À§Ä¡ÇÑ ³ª¼± ºÎºÐ¿¡¼­ 2°³ÀÇ ¾Æ¹Ì³ë»ê À§Ä¡¸¦ È®ÀÎÇß´Ù. À̵é À§Ä¡µé¿¡¼­ÀÇ Ä¡È¯ÀÌ Ã˸ŠȰ¼ºÀ» Áõ°¡½ÃÄ×À» »Ó ¾Æ´Ï¶ó ¼ö¿ë °¡´ÉÇÑ ±âÁúÀÇ ¹üÀ§¸¦ À¯ÀÇÇÏ°Ô ³ÐÇû´Ù. ¶Ç ´Ù¸¥ ¼º°øÀûÀÎ »ýü Ã˸ŠÀç¼³°è ÁßÀÇ Çϳª´Â JanuviaTM (Sitagliptin phosphate) °øÁ¤À» À§ÇÑ ATA-117 D-¾Æ¹Ì³ë»ê ¾Æ¹Ì³ë ÀüÀÌÈ¿¼ÒÀÇ °³¹ßÀÌ´Ù (Savile et al. 2010). Savile µîÀº transition state µµÅ·À» ÅëÇؼ­ semi-rational designÀ» »ç¿ëÇÏ¿© ¸ñÀû ±âÁú¿¡ ´ëÇÑ È°¼ºÀ» °³¼±ÇÏ¿© Ç¥Àû ±âÁúÀ» ¾Æ¹Ì³ëÈ­ ÇÒ ¼ö ÀÖ´Â È¿¼Ò¸¦ ¸¸µé¾î ³Â´Ù. ProSARÀ» ÅëÇÑ ¸î Â÷·ÊÀÇ Ãß°¡ÀûÀΠǥÀû ¹× ¹«ÀÛÀ§ µ¹¿¬º¯ÀÌ À¯¹ß ÈÄ¿¡ »ê¾÷Àû »êÃâ ¹× ¿î¿µ Á¶°ÇÀ» À§ÇØ ¼³°èµÈ È¿¼Ò°¡ °³¹ßµÇ¾ú´Ù. ±Ã±ØÀûÀ¸·Î ÃÖÁ¾ È¿¼Ò´Â È°¼º ºÎÀ§ ÁÖÀ§ ¹× ÀÌ·®Ã¼ ÀÎÅÍÆäÀ̽º ¸ðµÎ¿¡ 27°³ÀÇ µ¹¿¬º¯À̸¦ ÇÔÀ¯ÇÏ¿´´Ù. ¶ÇÇÑ Codexis´Â ¼º°øÀûÀ¸·Î semi-rational designÀ» Àû¿ëÇÏ¿© ¸î °¡Áö ÄÉÅä ȯ¿ø È¿¼ÒÀÇ È°¼º°ú °Å¿ï»ó ¼±ÅüºÀ» Çâ»ó½ÃÄѼ­ »ê¾÷ÀûÀ¸·Î ÀûÀýÇÑ ±âÁúÀ» Á¦Á¶ÇÏ¿´À¸¸ç, ÀÌ °úÁ¤ Áß¿¡ °á°ú·Î ³ª¿À´Â Ã˸ŵµ ¿øÇÏ´Â »ê¾÷Àû ¹ÝÀÀ Á¶°ÇÀ» ÇâÇؼ­ ÃÖÀûÈ­ µÇ¾ú´Ù (Ma et al. 2010, Liang et al. 2010, Huisman et al. 2010).

 

- Computational È¿¼Ò Àç¼³°è
Computational ´Ü¹éÁú ¼³°è ¾Ë°í¸®ÁòÀÇ Áøº¸´Â °¡»ó ȯ°æ¿¡¼­ÀÇ ¸ðµ¨¸µÀ» »ýü Ã˸ÅÀÇ Á¶ÀýÀ» À§ÇÑ ¸Å¿ì À¯¸ÁÇÑ Àü·«À¸·Î ¸¸µé¾ú´Ù. º¥Ä¡¿¡¼­ÀÇ ¼­¿­ º¯°æ°ú Á¶ÇÕÀû ¶óÀ̺귯¸® Áغñ¿¡ ´ëÇÑ ¾È³»·Î ÁøÈ­Àû Á¤º¸¿¡ ÀÇÁ¸ÇÏ´Â ´ë½Å computational ¹æ¹ýÀº ȸÀü À̼ºÁúü ¶óÀ̺귯¸®¿Í ¹éº» ÀçÆí¼ºÀ» »ç¿ëÇÏ´Â °ÍÀ» ÅëÇؼ­ Àü¹ÝÀû ´Ü¹éÁú ±¸Á¶¿¡ ´ëÇÑ ¾Æ¹Ì³ë»ê º¯ÀÌÀÇ ¿¡³ÊÁöÇÐÀ» È¿°úÀûÀ¸·Î Ãß»êÇÒ ¼ö ÀÖÀ¸¹Ç·Î ½ÇÇè¿¡ ÀÇÇÑ ´Ü¹éÁú °øÇÐÀ» ´ÜÁö ¸î °³ÀÇ ÇÕ¸®Àû ¼³°èÀÇ Æò°¡·Î Ãà¼ÒÇÑ´Ù. È¿¼ÒÀÇ ±âÁú ƯÀ̼ºÀ» °³Á¶ÇÒ ¼ö ÀÖ´Â ÀÌ ¿¹Ãø ƲÀÇ ´É·ÂÀº µÎ ±×·ì¿¡ ÀÇÇØ ÃÖ±Ù¿¡ Á¦½ÃµÇ¾ú´Ù. Chen µîÀº ÀڽŵéÀÇ K* ¾Ë°í¸®ÁòÀ» »ç¿ëÇÏ¿© ºñ ¸®º¸¼Ø ÆéƼµå ÇÕ¼º È¿¼Ò gramicidin S synthetase AÀÇ Æä´Ò¾Ë¸®´Ñ ¾Æµ¥´ÒÈ­ ¿µ¿ªÀÇ ±âÁú ƯÀ̼ºÀ» º¯°æÇß´Ù (Chen et al. 2009). »õ·Î¿î ±âÁú·Î Leu À̳ª ÀüÇϸ¦ ¶ì´Â ¾Æ¹Ì³ë»ê Arg, Lys, Glu ¶Ç´Â Asp Áß Çϳª¸¦ Ç¥ÀûÀ¸·Î ÇÏ´Â ÃÖÃÊÀÇ ½Ã¹Ä·¹À̼ÇÀº °áÇÕ Æ÷ÄÏÀÇ ¾ÈÂÊ¿¡ ±ò·Á ÀÖ´Â 7°³ÀÇ Àܱ⿡ ÁýÁßÇß´Ù (Fig. 3A). Leu¿¡ ´ëÇؼ­´Â 7°³ÀÇ À§Ä¡µé Áß 2°³¿¡¼­ÀÇ µ¹¿¬º¯ÀÌ°¡ kcat/KMÀ» 20¹è ´õ ³ô°Ô ÇÏ°í, Phe¿¡ ´ëÇÑ Ã˸ŠȿÀ²À» 30¹è °¨¼Ò½ÃÄѼ­ ¾Æµ¥´ÒÈ­ ¿µ¿ªÀÇ ±âÁú ƯÀ̼ºÀ» È¿°úÀûÀ¸·Î º¯°æÇÏ¿´´Ù. ÀÌÈÄ¿¡, ´Ü¹éÁú ±¸Á¶ÀÇ ´Ù¸¥ ºÎºÐ¿¡¼­ÀÇ µ¹¿¬º¯ÀÌ°¡ Ž±¸µÇ¾úÀ¸¸ç, ±×¸¦ ÅëÇØ È¿¼Ò È°¼ºÀ» ÇöÀúÈ÷ ³ôÀÎ °á°ú¸¦ ¾ò¾ú´Ù. ¶ÇÇÑ computational È¿¼Ò Àç¼³°è°¡ °³º°ÀûÀÎ ¾Æ¹Ì³ë»ê ġȯ¿¡ Á¦ÇÑµÉ ÇÊ¿ä°¡ ¾ø°í ·çÇÁ ¿µ¿ª ÀüüÀÇ ±³Ã¼¿¡ Àû¿ëµÉ ¼ö ÀÖ´Ù´Â ÈǸ¢ÇÑ ¼³¸íÀÌ Murphy µî¿¡ ÀÇÇØ º¸°íµÇ¾ú´Ù. (Murphy et al. 2009). ¹ÚÅ׸®¾Æ ½ÃÅä½Å Å»¾Æ¹Ì³ë È¿¼Ò¿¡¼­ ¾à°£ÀÇ ¿µ°¨À» ¾òÀº ÀúÀÚµéÀº ÀÚ»ì À¯ÀüÀÚ ¿ä¹ý¿¡¼­ÀÇ ÀáÀçÀûÀÎ Àû¿ëÀ» À§Çؼ­ ½ÃÅä½Å ƯÀ̼º Àΰ£ ±¸¾Æ´Ñ Å»¾Æ¹Ì³ë È¿¼Ò (hGDA) º¯Á¾À» »ý¼ºÇÏ´Â °ÍÀ» ¸ñÇ¥·Î hGDAÀÇ È°¼º ºÎÀ§ ·çÇÁ ¿µ¿ªÀÇ ¸®¸ðµ¨¸µÀ» À§Çؼ­ Rosetta ¼³°è ¾Ë°í¸®ÁòÀ» »ç¿ëÇÏ¿´´Ù. ·çÇÁ ±æÀÌ¿Í ¾Æ¹Ì³ë»ê ±¸¼ºÀÇ µ¿½ÃÀû º¯ÀÌ °¡»ó ȯ°æ¿¡¼­ÀÇ ¸ðµ¨¸µÀ» ÅëÇØ »õ·Î¿î ¼­¿­ÀÌ È®ÀεǾú´Âµ¥, ±×°ÍÀº ammelide (½ÃÅä½Å¿¡ ´ëÇØ °í¾ÈµÈ Áß°£Ã¼)¿¡ ´ëÇÑ È°¼ºÀ» 100 ¹è ³ôÀÌ°í ±¸¾Æ´Ñ Å»¾Æ¹Ì³ëÈ­¸¦ ³× ÀÚ¸´¼ö ¹è ¸¸Å­ °¨¼Ò½ÃÄ×´Ù (Fig. 3B).  ¶Ç ´Ù¸¥ ¼º°øÀûÀÎ °á°ú´Â Baker ½ÇÇè½Ç¿¡ ÀÇÇÑ È°¼º ºÎÀ§ÀÇ computational ¼³°è¸¦ Æ÷ÇÔÇÑ´Ù. ±×µéÀº Rosetta ¾Ë°í¸®ÁòÀ» »ç¿ëÇÏ¿© Kemp ¹èÁ¦ È¿¼Ò (Khersonsky et al. 2010, Alexandrova et al. 2008)¿Í Diels-Alderase (Siegel et al. 2010)¸¦ Æ÷ÇÔÇÏ´Â »õ·Î¿î »ýü Ã˸Ÿ¦ ¼º°øÀûÀ¸·Î ¼³°èÇß´Ù. ÀÌ·¯ÇÑ Ã˸ŵéÀº ±¸Á¶–±â´É °ü°è¿¡ ´ëÇÑ ÇöÀç±îÁöÀÇ ÀÌÇØ¿¡ ÀÌÀǸ¦ Á¦±âÇϸç ÀÚ¿¬¿¡¼­ ¹ß°ßµÇÁö ¾Ê´Â Ã˸Ÿ¦ ¼³°èÇÏ´Â ´Ü¹éÁú°øÇÐÀÚÀÇ ´É·ÂÀ» À¯ÀÇÇÏ°Ô Çâ»ó½ÃŲ´Ù.

Fig. 3. Computational È¿¼Ò Àç¼³°è. (A) µ¹¿¬º¯À̵é (ºÓÀº»ö)Àº ÀÛÀº ¼Ò¼ö¼º (Leu) ¶Ç´Â ÀüÇϸ¦ ¶í Ãø¼â¸¦ °¡Áø ¾Æ¹Ì³ë»ê(Arg)¿¡ ´ëÇÑ phenylalanine adenylation domainÀÇ ±âÁúƯÀ̼ºÀ» º¯È­½ÃÅ´. (B) Àΰ£ guanosine deaminase È°¼ººÎÀ§ ³» loop ¿µ¿ª(ºÓÀº»ö)ÀÇ engineeringÀº ammelide-specific deaminase¸¦ Á¦Á¶ÇÔ.


3. °íÂû
°¡»óȯ°æ ¶Ç´Â ±¸Á¶ ±â¹Ý ¹æ¹ýÀÇ È°¿ëÀÌ È¿°úÀû ´Ü¹éÁú °³·®À» À§ÇÑ ¿¹ÃøÀ» °¡´ÉÇÏ°Ô Çϸç ÀÌ°ÍÀº ½Ã½ºÅÛÀÇ º¹À⼺À» À¯ÀÇÇÏ°Ô ÁÙÀÏ ¼ö ÀÖ°í ´õ ÀÛ°í ±â´ÉÀûÀ¸·Î dzºÎÇÑ ¶óÀ̺귯¸®ÀÇ Á¦ÀÛÀ» °¡´ÉÇÏ°Ô ÇÑ´Ù. Directed evolutionÀÌ ¾ÆÁ÷µµ ÀÌ ÁýÁßµÈ ¶óÀ̺귯¸®¿¡¼­ ¼º´ÉÀÌ ÁÁÀº È帵éÀ» È®ÀÎÇÏ´Â °¡Àå È¿°úÀûÀÎ ½ÇÇè Àü·«ÀÌÁö¸¸ ÀÌ¹Ì »õ·Î¿î ¼³°è Àü·«°ú ±â¼úÀû Áøº¸°¡ ÀüÅëÀûÀÎ ÇÁ·ÎÅäÄݷκÎÅÍ ¹þ¾î³ª±â ½ÃÀÛÇÑ °ÍÀ» ÀǹÌÇÑ´Ù. Áï, ÃÖ±Ù semi-rational design ¶Ç´Â designed evolution ¿¡¼­ÀÇ ¹æ¹ý·ÐÀû Áøº¸´Â ´Ü¹éÁú ¿¬±¸Àڵ鿡°Ô »ýü Ã˸Ÿ¦ Á¶ÀÛÇÏ´Â °­·ÂÇÏ°í È¿°úÀûÀÎ »õ·Î¿î Àü·«À» Á¦°øÇÏ°í ÀÖ´Ù. ÀÌ¿Í°°ÀÌ ±¸Á¶ ±â¹Ý rational design ¶Ç´Â computational ´Ü¹éÁú ¼³°è ±â¹ýÀÌ °³º° ±â¼ú·Î¼­ ´Ü¹éÁú °øÇÐÀÚµéÀÌ »ýü °íºÐÀÚ¸¦ Á¶ÀÛÇÏ´Â ¹æ¹ýÀ» ±Ùº»ÀûÀ¸·Î º¯È­½ÃÄ×Áö¸¸ ´Ü¹éÁú °øÇÐÀ» À§ÇÑ ¹æ¹ýÀ¸·Î¼­ directed evolutionÀ» ¿Ïº®ÇÏ°Ô ´ëüÇÏÁö´Â ¸øÇÒ °ÍÀ¸·Î Àü¸ÁµÇ°í ÀÖ´Ù. ±× ´ë½Å¿¡ ´Ü¹éÁú °øÇÐ ¿¬±¸ÀÚµéÀº °¢ Àü·«ÀÇ º¸¿Ï¼ºÀ» ÀνÄÇÏ°í È¿¼ÒÀÇ º¸´Ù È¿°úÀûÀÎ Á¶ÀÛÀ» À§Çؼ­ À̵éÀÇ ÅëÇÕ ¶Ç´Â À¶ÇÕÀ» ¼ö¿ëÇØ¾ß ÇÒ °ÍÀ¸·Î »ç·áµÈ´Ù. ±Ã±ØÀûÀ¸·Î´Â ´ë±Ô¸ð ¼±º° Àåºñ¿¡ ´ú ÀÇÁ¸ÇÏ´Â °Í°ú ´õ ³ôÀº ¼Ò¸ðµÈ ÀÚ¿ø ´ÜÀ§ ´ç °³¼±À² ¶Ç´Â ÀûÁß·üÀÌ ´Ü¹éÁú°øÇÐ ¿¬±¸ÀÇ ÇâÈÄ ¹æÇâÀ» À¯µµÇÒ °ÍÀ¸·Î Àü¸ÁµÈ´Ù.

 

4. Âü°í¹®Çå
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Liang J, Mundorff E, Voladri R, Jenne S, Gilson L, Conway A, Krebber A, Wong J, Huisman G, Truesdell S et al.: Highly enantioselective reduction of a small heterocyclic ketone: biocatalytic reduction of tetrahydrothiophene-3-one to the corresponding (R)-alcohol. Org Process Res Dev 2010, 14:188-192.
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