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       À±¿©ÁØ        2013.09.02 09:47        15114
´Ù¿î·Îµå : ¹æ¼±±Õ_ÀÌÁ¾¼÷ÁÖ_»ý»ê½Ã½ºÅÛÀÇ_¿¬±¸_µ¿Çâ(ÀÌÈ­¿©´ë À±¿©ÁØ).pdf(191 Kb)
 

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1. Introduction

 

ÀÚ¿¬°è¿¡ Á¸ÀçÇÏ´Â ¼ö¸¹Àº ¹Ì»ý¹° Áß ¹æ¼±±Õ (Streptomyces)Àº ´ëÇ¥ÀûÀÎ ±×·¥¾ç¼º (Gram-positive) Åä¾ç¹Ì»ý¹°·Î¼­ ÇöÀç±îÁö º¸°íµÈ Ç×»ýÁ¦ Áß ¾à 60% ÀÌ»óÀ» »ý»êÇϸç, Ç×»ýÁ¦ ÀÌ¿Ü¿¡µµ ¸é¿ª¾ïÁ¦Á¦, Ç×¾ÏÁ¦, Ç×Áø±ÕÁ¦, Á¦ÃÊÁ¦, ´ç´¢º´Ä¡·áÁ¦, Ç×±â»ýÃæÁ¦ µîÀÇ ´Ù¾çÇÑ »ý¸®È°¼º¹°ÁúÀ» »ý»êÇÏ´Â ¸Å¿ì ¸Å·ÂÀûÀÎ ¹Ì»ý¹°ÀÌ´Ù. ±×·¯³ª »õ·Î¿î »ý¸®È°¼º¹°ÁúÀ» ¹ß°ßÇϱâ À§ÇÑ ´Ù¾çÇÑ ³ë·Â¿¡µµ ºÒ±¸ÇÏ°í, ÃÖ±Ù ¸î ³â µ¿¾È ¹æ¼±±ÕÀ¸·ÎºÎÅÍ »õ·Î¿î »ý¸®È°¼º¹°ÁúÀÇ ¹ß°ßÀº °¨¼ÒÇÏ°í ÀÖ´Ù. ¶ÇÇÑ ÀÌµé »ý¸®È°¼º¹°ÁúÀ» »ý»êÇÏ´Â ¾ß»ý »ý»ê±ÕÁÖÀÇ À¯ÀüÀÚ Á¶ÀÛ°ú ¹è¾çÀÌ ¾î·Á¿ï °æ¿ì ¹× À¯ÀüÀÚ¿øÀÇ ½ÇÁúÀû È°¿ëÀ» À§Çؼ­´Â È®º¸µÈ À¯Àüü Á¤º¸¸¦ ¹ÙÅÁÀ¸·Î ´ë·®»ý»êÀ» °¡´ÉÇÏ°Ô ÇÏ´Â º¸ÆíÀûÀÎ ±â¼úÀÇ °³¹ßÀÌ ÇÊ¿äÇÏ´Ù. °íÀüÀûÀÎ È­ÇÐÀû ÇÕ¼º¹ýÀÌ ¾Æ´Ñ, »ýÇÕ¼º °úÁ¤À» ÀÌÇØÇÏ°í À̸¦ ÀÌ¿ëÇÏ¿© ±¸Á¶º¯Çü °³·®½Å¾àÀ» °³¹ßÇÒ ¼ö ÀÖ´Â ¡®ÀÌÁ¾¼÷ÁÖ »ý»ê½Ã½ºÅÛ¡¯ÀÌ ÇØ°á ¹æ¾ÈÀÌ µÉ ¼ö ÀÖ´Ù. ƯÈ÷ »ê¾÷ÀûÀ¸·Î Áß¿äÇÑ ´ëÇ¥Àû ¹æ¼±±Õ Áß ±ØÈ÷ ÀϺθ¸ À¯ÀüÀÚ Á¶ÀÛÀÌ °¡´ÉÇϹǷÎ, À¯¿ë »ý¸®È°¼º¹°Áú »ýÇÕ¼º À¯ÀüÀÚ¸¦ À¯ÀüÀÚ Á¶ÀÛÀÌ ¿ëÀÌÇÑ ÀÌÁ¾¼÷ÁÖ¿¡ µµÀÔÇÏ°í ¹ßÇöÇÏ´Â ±â¼ú °³¹ßÀÌ ÇÊ¿äÇÏ´Ù (±×¸² 1).

 

±×¸² 1. ÀÌÁ¾¼÷ÁÖ »ý»ê½Ã½ºÅÛÀÇ °³¹ß

 

È¿°úÀûÀÎ ÀÌÁ¾¼÷ÁÖ »ý»ê½Ã½ºÅÛÀÇ °³¹ßÀ» À§Çؼ­´Â ¾ÈÁ¤µÈ ¹ßÇöº¤ÅÍ, ÀûÇÕÇÑ ÀÌÁ¾¼÷ÁÖÀÇ ¼±Á¤, »ý¸®È°¼º¹°Áú »ýÇÕ¼º °æ·ÎÀÇ ÀÌÇØ, ±×¸®°í ¸¶Áö¸·À¸·Î ÀÌÁ¾¼÷ÁÖ »ý»ê½Ã½ºÅÛÀÇ ¾ÈÁ¤Àû ¹ßÇöÀ» À§ÇÑ ÃÖÀûÈ­µÈ ¹æ¹ýÀÇ °í·Á°¡ ÇÊ¿äÇÏ´Ù. ÀÌ·¯ÇÑ ÀÌÁ¾¼÷ÁÖ »ý»ê½Ã½ºÅÛÀ» ÀÌ¿ëÇÑ ÀÌÂ÷´ë»ç»ê¹°ÀÇ »ý»ê¿¡ À־ À¯ÀüÀÚ Á¤º¸°¡ Àß ¾Ë·ÁÁ® ÀÖ°í, Àüü genome sequencingÀÌ ¿Ï·áµÇ¾î ÀÖ¾î, ´ë»çüµéÀÌ Àß ¾Ë·ÁÁ® ÀÖ´Â ¹æ¼±±Õ Streptomyces coelicolor, S. lividans, S. albus J1074, S. avermitilis µîÀÌ ÀÌÂ÷´ë»ç»ê¹°ÀÇ »ý»ê¿¡ ÀûÇÕÇÑ host·Î¼­ ÃÖÀûÈ­µÈ ¹ßÇö ½Ã½ºÅÛÀ» °®Ã߱⿡ ¸¹Àº ÀåÁ¡À» °¡Áö°í ÀÖ´Ù. ÀÌ·¯ÇÑ ÀÌÀ¯·Î ÇöÀç ¸¹Àº ¿¬±¸½Ç°ú »ê¾÷ ¼Ó¿¡¼­ ÀÌÁ¾¼÷Áַμ­ »ç¿ëµÇ°í ÀÖ´Ù.  


±×¸² 2. º» ¿¬±¸½Ç¿¡¼­ ¹æ¼±±Õ ÀÌÁ¾¼÷ÁÖ »ý»ê ½Ã½ºÅÛÀ» ÅëÇÏ¿© »ý»êµÈ »ý¸®È°¼º¹°Áú

 

2. ¹æ¼±±Õ¿¡¼­ ¹æ¼±±ÕÀ¸·ÎÀÇ ÀÌÁ¾¼÷ÁÖ ¹ßÇö

 

ÀϹÝÀûÀÎ cloning host·Î S. albus J1074´Â Salas group¿¡¼­ óÀ½ »ç¿ëÇÏ¿© fredericamycinÀÇ ÀÌÁ¾¼÷ÁÖ ¹ßÇö¿¡ »ç¿ëµÇ¾ú´Ù. S. griseus°¡ »ý»êÇÏ´Â Ç×»ýÁ¦ÀÎ fredericamycinÀÇ »ýÇÕ¼º À¯ÀüÀÚÁý´ÜÀ» ÀÌÁ¾¼÷ÁÖ S. albus J1074¿¡¼­ high copy number plasmid¸¦ »ç¿ëÇÏ¿© ¹ßÇö½ÃÄ×À» ¶§ 120 mg/L°¡ »ý»êµÇ°í [1], single copy number ¥õC31-integrationÀ¸·Î 132 mg/L°¡ »ý»êµÇ¾ú´Ù [2]. ¹Ý¸é¿¡ µ¿ÀÏÇÑ fredericamycin pathway¸¦ S. lividans¿¡¼­ ¥õC31 attB site¸¦ ÀÌ¿ëÇÏ¿© ¹ßÇö½ÃÄ×À» ¶§´Â »ý»êÀÌ µÇÁö ¾Ê¾Ò´Ù [2].


S. coelicolor¿Í S. lividans´Â genomic sequence°¡ µÎ ¹æ¼±±Õ ¸ðµÎ ¹àÇôÁ® ÀÖÀ¸¸ç À¯ÀüÀÚÁ¶ÀÛ ¹æ¹ý ¿ª½Ã Àß ¾Ë·ÁÁ® ÀÖ¾î ¿¬±¸½Ç¿¡¼­ ÀÚÁÖ »ç¿ëµÇ´Â ÀÌÁ¾¼÷ÁÖ ¹ßÇö¿ë hostÀÌ´Ù. NovobiocinÀº S. niveus¿¡¼­ »ý»êµÇ´Â Ç×»ý¹°Áú·Î¼­ ¥õC31 attB site¸¦ ÀÌ¿ëÇÏ¿© S. coelicolor M512¿Í S. lividans TK24¿¡¼­ °¢°¢ ÀÌÁ¾¼÷ÁÖ ¹ßÇö ÇÏ¿´À» ¶§ Àç¹ÌÀÖ´Â °á°ú¸¦ ³ªÅ¸³»¾ú´Ù. °¢°¢ÀÇ »ý»ê·®ÀÌ 31 mg/L¿Í 1 mg/L·Î Çö°ÝÇÑ Â÷À̸¦ º¸¿´´Ù [3]. ´õ ³ª¾Æ°¡ S. coelicolor M512¿¡ ÀÌÁ¾¼÷ÁÖ ¹ßÇöÀ» ÇÏ°í, ¹è¾ç Á¶°Ç optimize¸¦ ½Ç½ÃÇÏ¿´À» ¶§ Ãʱ⠻ý»ê·® 31 mg/L¿¡¼­ 54 mg/L·Î Áõ°¡ÇÏ°í, À¯ÀüÀÚ Á¶ÀÛÀ» ÅëÇÏ¿© positive regulator ´Ü¹éÁúÀ» ¾ÏȣȭÇÏ°í ÀÖ´Â À¯ÀüÀÚ¸¦ °ú¹ßÇö½ÃÄÑ ÁÖ¾úÀ» ¶§ 163 mg/L·Î Áõ°¡ÇÏ´Â °á°ú¸¦ ³ªÅ¸³»¾ú´Ù [4].

 

º» ¿¬±¸ÆÀÀº ÀÌÁ¾¼÷ÁÖ »ý»ê½Ã½ºÅÛÀÇ host·Î S. venezuelae¸¦ ¼±Á¤ÇÏ°í, pikromycinÀÇ aglycon »ýÇÕ¼º¿¡ ÇÊ¿äÇÑ À¯ÀüÀÚµé°ú deoxysugarÀÎ desosamine¿¡ ÇÊ¿äÇÑ À¯ÀüÀÚµéÀ» Á¦°ÅÇÑ µ¹¿¬º¯ÀÌÁÖ¸¦ Á¦ÀÛ¡¤°³¹ßÇÏ¿´´Ù. ¶ÇÇÑ °Å´ë»ýÇÕ¼º À¯ÀüÀÚ ¹ßÇö¿¡ ÀûÇÕÇÑ E. coli-Streptomyces shuttle vector·Î¼­ µ¿½Ã ´ÙÁß ¹ßÇöÀÌ °¡´ÉÇÑ replication vector¿Í integration vector¸¦ °í¾ÈÇÏ°í, ¿Ü·¡ »ýÇÕ¼º À¯ÀüÀÚÁý´ÜÀÇ È¿À²Àû ¾ÈÁ¤Àû ¹ßÇöÀ» À§ÇÑ µ¿½Ã ´ÙÁß º¤ÅÍ Á¶ÇÕÀ» ÃÖÀûÈ­ ÇÏ¿´´Ù. À̸¦ ÅëÇÏ¿© S. fradiae À¯·¡ Ç×»ýÁ¦ÀÎ tylosinÀÇ ¾à 50 kb¿¡ ´ÞÇÏ´Â °Å´ë À¯ÀüÀÚ Áý´ÜÀ» 2Á¾ µ¿½Ã ¹ßÇöÀÌ °¡´ÉÇÑ º¤ÅÍ ½Ã½ºÅÛ¿¡ tylosin polyketide synthase (Tyl PKS)¸¦ ³ª´©¾î Ŭ·Î´×ÇÑ ÈÄ, PKS¸¦ Á¦°ÅÇÑ S. venezuelae µ¹¿¬º¯ÀÌÁÖ ³»¿¡¼­ ¹ßÇöÇÏ¿© tylactone 0.5 mg/L°ú desosaminyl tylactoneÀ» ¼º°øÀûÀ¸·Î »ý»êÇÏ¿´´Ù [5].

 

¶ÇÇÑ, °áÇÙ±Õ°ú Æó·Å±Õ µîÀÇ Ä¡·á¿¡ »ç¿ëµÇ¾î ¿Â °¡Àå ¿À·¡µÈ Ç×»ýÁ¦ Áß ÇϳªÀÎ kanamycinÀ» »ý»êÇÏ´Â Åä¾ç¹Ì»ý¹° S. kanamyceticus´Â À¯ÀüÀÚ Á¶ÀÛÀÌ °ÅÀÇ ºÒ°¡´ÉÇØ, kanamycinÀÇ »ýÇÕ¼º °æ·Î ±Ô¸íÀº Àü ¼¼°è °úÇÐÀڵ鿡°Ô Ç®¸®Áö ¾Ê´Â ¼÷Á¦¿´´Ù. º» ¿¬±¸ÆÀÀº kanamycin ÇÕ¼º¿¡ °ü¿©ÇÏ´Â ¸ðµç À¯ÀüÀÚ¸¦ ¼±º°ÇÑ ÈÄ, À̵éÀ» ¿©·¯ °³ÀÇ À¯ÀüÀÚ Á¶°¢À¸·Î Àß¶ó ·¹°í ºí·Ïó·³ Á¶¸³ÇÏ¿©, À¯ÀüÀÚ Á¶ÀÛÀÌ ½¬¿î ÀÌÁ¾¼÷ÁÖÀÎ S. venezuelae¿¡¼­ ¹ßÇöÇÏ°í, ´Ù¾çÇÏ°Ô Á¶ÇÕµÈ À¯ÀüÀÚ ¼¼Æ®¿¡¼­ ¸¸µé¾î³½ ¹°ÁúÀ» Çϳª¾¿ È®ÀÎÇÏ´Â ¹æ¹ýÀ¸·Î kanamycin »ýÇÕ¼º °æ·Î¸¦ ¹àÇô³»¾ú´Ù [6].

 

3. ½Ä¹°¿¡¼­ ¹æ¼±±ÕÀ¸·ÎÀÇ ÀÌÁ¾¼÷ÁÖ ¹ßÇö

 

½Ä¹° À¯·¡ÀÇ polyphenol È­ÇÕ¹°Àº Ç×»êÈ­, ¾Ï¿¹¹æ, Ç×¾Ï, Ç×õ½Ä, Ç׿°Áõ, Ç×±Õ µîÀÇ ´Ù¾çÇÑ »ý¸®È°¼ºÀ» °®À¸¸ç, ±× Áß flavonoid¿Í stilbene È­ÇÕ¹°Àº °¢Á¾ ±â´É¼º ½ÄÇ°, È­ÀåÇ° ¹× ÀǾàÇ° °³¹ßÀÇ ÀáÀç·ÂÀÌ ÀÖ´Â »õ·Î¿î ÀÚ¿øÀ¸·Î Áß¿äÇÑ ¿¬±¸ ´ë»óÀÌ´Ù.

 

ÀϺ» µ¿°æ´ëÀÇ Horinouchi ±×·ìÀº E. coli¸¦ ÀÌÁ¾¼÷ÁÖ·Î »ç¿ëÇÏ¿© yeastÀÎ Rhodotorula rubraÀÇ PALÀÌ tyrosineÀ» ±âÁú·Î »ç¿ëÇÏ¿© coumaric acid¸¦ »ý»êÇÒ ¼ö ÀÖ´Ù´Â »ç½ÇÀ» ÀÌ¿ëÇÏ¿©, À̸¦ ¹æ¼±±ÕÀÎ S. coelicolor A3(2)ÀÇ 4-coumarate:CoA ligase (ScCCL), licorice plantÀÎ Glycyrrhiza echinataÀÇ CHSÀÇ À¯ÀüÀÚµé°ú Á¶ÇÕ ¹ßÇöÇÏ¿© flavonoid È­ÇÕ¹° Áß °¡Àå °£´ÜÇÑ ±¸Á¶ÀÇ flavanoneÀÎ naringenineÀ» ¼Ò·® »ý»êÇϴµ¥ ¼º°øÇÏ¿´´Ù [7]. ¶ÇÇÑ ¹Ì±¹ ¹Ì³×¼ÒŸ ´ëÇÐÀÇ Schmidt-Dannert ±×·ìÀº À¯»çÇÑ ¹æ¹ýÀ» »ç¿ëÇÏ¿´À¸³ª, PALÀ» Rhodobacter shpaeroidesÀÇ tyrosine ammonia lyase (TAL)·Î, ³ª¸ÓÁö À¯ÀüÀÚµéÀº Arabidopsis thaliana À¯·¡ÀÇ À¯ÀüÀÚµé·Î ´ëüÇÔÀ¸·Î½á Çâ»óµÈ »ý»ê¼ºÀ» º¸°íÇÏ¿´´Ù [8]. ´º¿åÁÖ¸³´ëÇÐÀÇ Koffas ±×·ìÀº È¿¸ðÀÎ Saccharomyces cerevisiaeÀ» ÀÌÁ¾¼÷ÁÖ·Î »ç¿ëÇÔÀ¸·Î½á »ý»ê¼ºÀ» Çâ»ó½Ãų ¼ö ÀÖ¾ú´Ù°í º¸°íÇÏ¿´À¸³ª [9], ÀÌµé ¿¬±¸µéÀº ÀçÁ¶ÇÕ ¹Ì»ý¹°À» ÀÌ¿ëÇÏ¿© flavonoid È­ÇÕ¹°ÀÇ »ý»ê °¡´É¼ºÀ» ÀÔÁõÇÏ¿´À¸³ª, »ê¾÷È­¸¦ À§Çؼ­´Â »ý»ê¼ºÀÌ ³·À¸¸ç, º¸´Ù ´Ù¾çÇÑ ±¸Á¶ÀÇ È­ÇÕ¹°ÀÇ »ý»êÀº ¼º°øÇÏÁö ¸øÇÏ¿´À¸¸ç, ¶ÇÇÑ E. coliÀÇ °æ¿ì´Â chalconeÀÇ »ýÇÕ¼º Àü±¸Ã¼ÀÎ malonyl-CoAÀÇ ¼¼Æ÷³» ³óµµ°¡ ³·¾Æ »ý»ê¼ºÀÌ ¶³¾îÁö´Â ±Ùº»ÀûÀÎ ´ÜÁ¡ÀÌ ÀÖ°í, S. cerevisiaeÀÇ °æ¿ì´Â ¿©·¯ °³ÀÇ »ýÇÕ¼ºÀ¯ÀüÀÚµéÀ» ¹ßÇö½ÃÅ°´Âµ¥ À¯¿ëÇÑ ´ÙÁß¹ßÇöº¤ÅÍ (multi-vector)ÀÇ ±¸ÇöÀÌ ¾î·Á¿î ´ÜÁ¡ÀÌ ÀÖ´Ù.

 

º» ¿¬±¸ÆÀÀº S. coelicolorÀÇ coenzyme A ligase (ScCCL)¿Í Arabidopsis thalianaÀÇ chalcone synthase (atCHS)¸¦ single ermE*¸¦ »ç¿ëÇÏ¿© S. venezuelae¿¡¼­ ¹ßÇöÇÏ¿© naringenin°ú pinocembrinÀÇ »ý»êÀ» È®ÀÎÇÏ¿´´Ù [10]. ¶ÇÇÑ ÀÌÁ¾¼÷ÁÖ¿¡ ÀûÇÕÇϵµ·Ï codon optimizeÇÏ¿© »ýÇÕ¼ºÇÑ flavone synthase I gene (Petroselium crispum)À» S. venezuelae¿¡¼­ ¹ßÇöÇÏ°í flavanonesÀ» ³Ö¾îÁÖ¾úÀ» ¶§, flavonesÀÌ »ý»êµÇ´Â °ÍÀ» È®ÀÎÇÏ¿´´Ù. Ãß°¡·Î µ¿ÀÏÇÑ ¹æ¹ýÀ¸·Î optimizeÇÑ ÇÕ¼º À¯ÀüÀÚ 3¥â-hydroxylase gene (Citrus siensis)°ú flavonol synthase gene (Citrus unshius)À» S. venezuelae¿¡¼­ ¹ßÇöÇÏ¿© flavonolsÀ» ¼º°øÀûÀ¸·Î »ý»êÇÏ¿´´Ù [11].

 

4. Åä¾ç¹Ì»ý¹° ¹× Çؾç¹Ì»ý¹°¿¡¼­ ¹æ¼±±ÕÀ¸·ÎÀÇ ÀÌÁ¾¼÷ÁÖ ¹ßÇö

 

Åä¾ç¹Ì»ý¹°ÀÎ myxobacteria Sorangium cellulosumÀ¸·ÎºÎÅÍ »ý»êµÇ´Â epothilneÀº Taxol°ú À¯»çÇÑ ÀÛ¿ëÀ» ÇÏÁö¸¸, ºÎÀÛ¿ëÀÌ Àû¾î ³»¼ºÀÌ ÀÖ´Â ¾Ï¼¼Æ÷¿¡ °­ÇÑ Ç×¾ÏÀÛ¿ëÀ» º¸¿© Â÷¼¼´ë Ç×¾ÏÁ¦·Î ´ëµÎµÇ°í ÀÖ´Ù. ±×·¯³ª ÀÚ¿¬»ý»ê±ÕÁÖÀÎ Sorangium cellulosumÀº ¼ºÀå¼Óµµ°¡ ¸Å¿ì ´À¸®°í (doubling time, 16h) »ý»ê¼ºµµ ¸Å¿ì ³·À¸¸ç, À¯ÀüÀÚ Á¶ÀÛÀÌ ¾î·Á¿ö À¯ÀüÀÚ Á¶ÀÛ¿¡ ÀÇÇÑ »ý»ê¼º Çâ»óÀ» ±â´ëÇϱ⠾î·Æ´Ù. ÀÌ·± ÀÌÀ¯¿¡¼­ ¸¹Àº ¿¬±¸ÆÀµéÀÌ ÀÌÁ¾¼÷ÁÖ »ý»ê½Ã½ºÅÛÀÇ °³¹ßÀ» ÁøÇàÇÏ°í ÀÖ´Ù. ¹Ì±¹ÀÇ Kosan Bioscience¿¡ ÀÇÇØ E. coli¿¡¼­ epothiloneÀ» ´ë»óÀ¸·Î ½ÃµµµÇ¾úÀ¸³ª, ¼öÀ²ÀÌ 1 ¥ìg/L ÀÌÇÏ·Î ±ØÈ÷ ³·¾Ò´Ù [12]. ¶ÇÇÑ µ¶ÀÏ Saarland ´ëÇÐÀÇ Rolf Müller groupÀº optimized synthetic geneÀ» ÀÌ¿ëÇÏ¿© ÀÌÁ¾¼÷ÁÖ Myxococcus xanthus¿¡¼­ epothiloneÀ» ¹ßÇöÇÏ¿© 100 ¥ìg/L¸¦ »ý»êÇÏ¿´´Ù [13].  ¹æ¼±±Õ¿¡¼­´Â º» ¿¬±¸ÆÀÀÌ À¯ÀüÀÚÀÇ È¿À²ÀûÀÎ ¹ßÇöÀ» À§ÇØ ´Ù¸¥ ¹æ¼±±Õ°ú ºñ±³ÇÏ¿© ¼ºÀå ¼Óµµ°¡ 2¹è ÀÌ»ó ºü¸£¸ç, À¯ÀüÀÚ Á¶ÀÛÀÌ ¿ëÀÌÇÏ¿© ÀÌÁ¾¼÷Áַμ­ °³¹ß °¡Ä¡°¡ ¸Å¿ì ³ôÀº S. venezuelae¸¦ ÀÌÁ¾¼÷ÁÖ·Î ¼±Á¤ÇÏ°í µ¹¿¬º¯ÀÌÁÖ¸¦ Á¦ÀÛÇÏ¿© °Å´ë »ýÇÕ¼º À¯ÀüÀÚ Áý´ÜÀÇ ¹ßÇö¿¡ ÀûÇÕÇÑ ´ÙÁß¹ßÇöº¤ÅÍ ½Ã½ºÅÛ (multi-vector system)À» ±¸ÃàÇÏ¿´´Ù. À̸¦ ÅëÇÏ¿© epothilone B ¾à 0.1 ¥ìg/L¿Í epothilone D 0.4 ¥ìg/L¸¦ »ý»êÇÏ¿´´Ù [14].

 

Çؾç õ¿¬È­ÇÕ¹°Àº ´Ù¾çÇÑ À¯¿ëÇÑ »ý¸®È°¼ºÀ» °¡Áö¹Ç·Î °æÁ¦Àû¡¤»ê¾÷Àû °¡Ä¡°¡ ¸Å¿ì ³ôÀ¸¸ç, ÇöÀç ¸¹Àº ¼öÀÇ È­ÇÕ¹°µéÀÌ ÁÖ·Î Ç×¾ÏÁ¦·Î¼­ ÀüÀÓ»ó ¶Ç´Â ÀÓ»ó½ÃÇè ÁßÀÓ. ±×·¯³ª º¸Åë ÇØ¾ç »ý¹°ÀÇ Á¶Á÷À¸·ÎºÎÅÍ È¸¼öÇÒ ¼ö ÀÖ´Â ¾çÀÌ ¸Å¿ì Á¦ÇÑÀûÀ̹ǷÎ, ÀÓ»ó½ÃÇè¿¡ ÇÊ¿äÇÑ ÃæºÐÇÑ È­ÇÕ¹°ÀÇ °ø±ÞÀÌ ¾î·Á¿ì¸ç, ÀÌ´Â Çؾç õ¿¬È­ÇÕ¹°·ÎºÎÅÍ ½Å¾à°³¹ßÀÇ °¡Àå Å« ¹®Á¦Á¡ÀÌ´Ù. ÀÌÀÇ ¿øÈ°ÇÑ °ø±ÞÀ» À§ÇÏ¿©, ´ë·® »ý»êÇÏ°íÀÚ ÇÏ´Â Çؾç õ¿¬¹°ÀÇ »ýÇÕ¼º À¯ÀüÀÚÁý´ÜÀ» ÇØ¾ç ¹Ì»ý¹°·ÎºÎÅÍ È®º¸ÇÏ°í À̸¦ À¯ÀüÀÚ Á¶ÀÛ ¹× ¹è¾çÀÌ ¿ëÀÌÇÑ ÀÌÁ¾¼÷ÁÖ¿¡¼­ ¹ßÇöÇÏ´Â ÀÌÁ¾¼÷ÁÖ »ý»ê½Ã½ºÅÛÀÇ °³¹ßÀº ÇʼöÀûÀÌ´Ù. ÇØ¾ç ³²Á¶¼¼±ÕÀÎ Moorea producens À¯·¡ »ý¸®È°¼º¹°ÁúÀÎ barbamide (¾à 28 kb)ÀÇ °Å´ë »ýÇÕ¼º À¯ÀüÀÚ Áý´ÜÀ» ÀÌÁ¾¼÷ÁÖ »ý»ê½Ã½ºÅÛÀ» ÀÌ¿ëÇÏ¿© »ý»ê¼º Çâ»ó ¹× À¯µµÃ¼ °³¹ß¿¡ ´ëÇÑ ¿¬±¸¸¦ ÁøÇàÇÏ¿©, barbamide °Å´ë »ýÇÕ¼º À¯ÀüÀÚ Áý´ÜÀ» S. venezuelae¿¡¼­ ÀÌÁ¾¼÷ÁÖ ¹ßÇöÇÏ¿© 4-O-demethylbarbamideÀÇ »ý»êÀ» È®ÀÎÇÏ¿© Çؾç õ¿¬¹°ÀÇ È¿À²Àû ¹Ì»ý¹° »ý»ê½Ã½ºÅÛÀÇ °³¹ß ¿¹·Î½á, ¿ÏÀüÇÑ marin cyanobacterial NRPS/PKSÀÇ Ã¹ ÀÌÁ¾¼÷ÁÖ ¹ßÇöÀÌ´Ù [15].

 

ÇöÀç º» ¿¬±¸ÆÀÀº S. venezuelae¸¦ ÀÌÁ¾¼÷ÁÖ·Î ¼±Á¤ÇÏ°í ÀÌÁ¾¼÷ÁÖ¿¡ codon optimizeµÈ epothilone »ýÇÕ¼º À¯ÀüÀÚ Áý´Ü°ú Çؾç¹Ì»ý¹° À¯·¡ cryptophycin »ýÇÕ¼º À¯ÀüÀÚ Áý´ÜÀ» ¹ßÇö, »ý»ê¼º Çâ»óÀ» À§ÇÑ ¿¬±¸¸¦ ÁøÇà ÁßÀÌ´Ù (±×¸² 3). 

 

±×¸² 3. S. venezuelae ÀÌÁ¾¼÷ÁÖ »ý»ê½Ã½ºÅÛÀ» ÅëÇÑ Epothilone°ú CryptophycinÀÇ »ý»ê

 

5. Âü°í¹®Çå

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[15] Kim EJ, Lee JH, Choi H, Pereira AR, Ban YH, Yoo YJ, Kim E, Park JW, Sherman DH, Gerwick WH, Yoon YJ. Heterologous production of 4-O-demethylbarbamide, a marine cyanobacterial natural product. Org Lett. 2012 Dec 7;14(23):5824-7.




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[1] [2] [3] [4] [5] [6] [7] [8]