못했던새로운방향족화합물을합성하는방법이다. 두번째접근방법을이용한연구는자연적으로생산되지않는방향족화합물의생산을가능케하기때문에이에대한관심이지속적으로증가하고있다. 본글에서는최근미생물을이용한방향족화합물생산에관한연구의동향에대하여소개하고자한다. 그림 1. 미생물을통해바이오매스로부터생

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미생물에서의방향족화합물생산을위한 대사공학연구의최근동향 Zi Wei Luo - KAIST Department of Chemical and Biomolecular Engineering PhD candidate Sang Yup Lee - KAIST Department of

대사공학과합성생물학의발전으로바이오연료, 유기산과아미노산등의화합물을효율적으로생산하는연구가진행되었고, 그중방향족화합물은의약품, 향료, 다양한플라스틱등을생산하기위한재료로사용되고있으며 ( 그림 1), 최근미생물의대사경로조작을위한목적화합물로서많은연구가진행되고있다.

1 미생물에서의방향족화합물생산을위한 대사공학연구의최근동향 Zi Wei Luo - KAIST Department of Chemical and Biomolecular Engineering PhD candidate Sang Yup Lee - KAIST Department of Chemical and Biomolecular Engineering Distinguished Professor 1. 개요 심각한기후변화와화석연료의고갈에대한대응책으로미생물을이용하여화석연료로부터생산되는화합물을생합성하기위한미생물대사공학기술은지난몇년간큰성장과발전을이뤘다. 대사공학과합성생물학의발전으로바이오연료, 유기산과아미노산등의화합물을효율적으로생산하는연구가진행되었고, 그중방향족화합물은의약품, 향료, 다양한플라스틱등을생산하기위한재료로사용되고있으며 ( 그림 1), 최근미생물의대사경로조작을위한목적화합물로서많은연구가진행되고있다. 미생물을이용하여방향족화합물을생산하기위해서는일반적으로두가지접근방법을이용한다. 첫번째는식물이나곰팡이와같은고등생물이자연적으로보유하고있는방향족화합물합성대사회로를도입시켜주는방법이고, 두번째는생물정보학, 시스템생물학, 합성생물학, 단백질공학, 오믹스기술등의발전을통해얻어진정보로부터자연계에서합성하지

못했던새로운방향족화합물을합성하는방법이다. 두번째접근방법을이용한연구는자연적으로생산되지않는방향족화합물의생산을가능케하기때문에이에대한관심이지속적으로증가하고있다. 본글에서는최근미생물을이용한방향족화합물생산에관한연구의동향에대하여소개하고자한다. 그림 1. 미생물을통해바이오매스로부터생산되는방향족화합물 2.

2 못했던새로운방향족화합물을합성하는방법이다. 두번째접근방법을이용한연구는자연적으로생산되지않는방향족화합물의생산을가능케하기때문에이에대한관심이지속적으로증가하고있다. 본글에서는최근미생물을이용한방향족화합물생산에관한연구의동향에대하여소개하고자한다. 그림 1. 미생물을통해바이오매스로부터생산되는방향족화합물 2. 방향족아미노산생산을위한전략 몇가지방향족화합물들 ( 예를들어, malonyl-coa 로부터유도되는 phloroglucinol) 을제외하고, 일반적으로방향족화합물은 shikimate 대사회로로부터유도되는 endogenous 전구체를사용하는대사회로를거쳐생산된다. 다양한방향족화합물을생산하기위한대사회로는일반적으로 aromatic amino acids (AAA) 생산대사회로를기반으로한다. 대장균내에는 L- tryptophan (L-TRP), -phenylalanine (L-PHE) 및 L- tyrosine (L-TYR) 생산대사회로 ( 그림 2) 가존재하며최근방향족아미노산생산량을증가시키기위한연구가많이진행되고있다. 방향족아미노산을생산하기위한대사공학적전략들은다음과같다. (i)

3 직접적인전구체인 phosphoenolpyruvate (PEP) 과 erythrose-4-phosphate (E4P) 의생산효율을증대 ; (ii) shikimate 대사회로의첫효소인 3-deoxy-D-arabinoheptulosonate-7-phosphate (DAHP) synthase 도입, (iii) transcriptional regulation 및 allosteric regulation 제거 ; (iv) rate-limiting 효소를탐색하고해결, (v) 경쟁대사회로를결실 ; (vi) 방향족화합물 export 강화 ; (vii) 방향족화합물분해유전자결실. 그림 2. 방향족아미노산생산대사회로

4 3. 다양한방향족화합물생산을위한대사경로제작 대사경로에서전구체로쓰이면서도독특한기능을하는대사체를다양하게확보하는것은 3-dehydroshikimate (3-DHS) 에서말단 AAA 산물에이르기까지기존에생산되고있거나생산될가능성이있는넓은범위의방향족화합물의생산을가능하게하는요소이다. Chorismate는강력하게조절되는대사분기에포함되어있어수많은방향족대사경로에서특히유용한전구체로쓰인다. 4-수산기의기능성이보존된페놀계열의화합물은 L-TYR 분기에서유래되며, 페놀, p-수산벤조산, 쿠마르산, 커피산, 페룰산, p-수산스티렌, 티로솔, 수산티로솔이이에포함된다. L-PHE 분기로부터뻗어나가는경로로는 2-페닐에탄올, 계피산스티렌, (S)-산화스티렌, (R)-1,2-페닐에타네디올, (S)-만델산과 (R)-만델산, 벤질알데히드와같은화합물을생산하기위한경로가개발되었다. L-TRP 분기에서는비교적그수는적지만 AAA경로에서페닐젖산, 페닐아세트산, L-DOPA, 비올라세인과디옥시비올라세인, 아베난스라아미드, 레스베라톨과같이고부가가치의화합물들이유래되었다. 방향족화합물의생산에관여하는대사경로개발에있어서최근에각광받는효율적인접근방법으로는대사경로의일련의여러모듈로나누는방법이있다. 최근에개발된주목받을만한기법으로는생물기반방향족화합물생산에있어서별개의다중경로를하나의최종산물을생산하기위해사용하는기법이다. 이렇듯다중경로를사용하면여러다른전구체와생산을돕는화학물질들을사용하여주요생산경로가지니는한계를뛰어넘기위한효과적인선택지를얻을수있게된다. 4. 고찰 이미알려진효소의기질특이성을조작하고합성생물학기법을이용함으로써다양한방향족화합물생합성경로의제작이용이해졌다. 이와같은방법으로기존에생물기반으로생산할수없었던방향족화합물의생산이가능해졌지만화합물의독성및값비싼전구체가문제점으로제시되고있다. 본문제들을해결하기위해급격한속도로성장해가고있는생명공학, 특히합성생물학과시스템생명공학의발달이효율적인대사회로의구축과정제기술의발전을촉진시켜방향족화합물생산에크게기여할것으로생각된다.

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