이용자는 아래의 조건을 따르는 경우에 한하여 자유롭게

(1)

저작자표시-비영리-변경금지 2.0 대한민국 이용자는 아래의 조건을 따르는 경우에 한하여 자유롭게

l 이 저작물을 복제, 배포, 전송, 전시, 공연 및 방송할 수 있습니다. 다음과 같은 조건을 따라야 합니다:

l 귀하는, 이 저작물의 재이용이나 배포의 경우, 이 저작물에 적용된 이용허락조건 을 명확하게 나타내어야 합니다.

저작권법에 따른 이용자의 권리는 위의 내용에 의하여 영향을 받지 않습니다. 이것은 이용허락규약(Legal Code)을 이해하기 쉽게 요약한 것입니다.

Disclaimer

저작자표시. 귀하는 원저작자를 표시하여야 합니다.

비영리. 귀하는 이 저작물을 영리 목적으로 이용할 수 없습니다.

변경금지. 귀하는 이 저작물을 개작, 변형 또는 가공할 수 없습니다.

(2)

ᙽ㻡⪥⨴㻡れᬄⓀ#

#

w

wGG To ¡ GGwG|G lG lGG

#

㨂㫆䞿G ╖㧻‶㦚G 㧊㣿䞲G 䗮⏖⪲⿖䎆G G 䕢⧒T䞮㧊✲⪳㔲⻺㯞㞢◆䞮㧊✲㦮G ㌳㌆G

#

534< ᫌ# ; ぜ#

#

⪤぀ᲈ㻡ᛘ# ᲈ㻡じ#

㿜㻡⩥Ⓞᙽ㻡✈#

㊄⪹⽸#

(3)

(4)

GG

hG

To ¡ G OoihsPG G G G G G

G G G SG SG G G G G G G

UG hG G G G GoihsSG G G G

G G G G UG oSG G G G G

GGGGGGGGGUG G

mG G SG G G G G GlUSG

GsT GGTGGOjhPSGGGUGuSGG

G G G G G G G G G G

GGGGGGGUG

G {G GoihsG G G G G G SG G G

G G G G G GlUUG pG G G XSG G

G GO{wsPGGjGGG GG GO{hsPG

G zG G G G G G lUG

UG{GGG GGGGzkzTwhnlG

GGGGXWGt^GGGGGWU_Gt^GGjhG

GXYGO_GLPUGpGGGYSG[U\GtGGoihsGO`WGLPGGGG\GtG G

GjhG G G G G jhG G OmjzPG G G jhG VGOljoPGGXYUG G

m SGGGXGGGYGGSGGGGWUW]G

tG GoihsG G \G tG G G OXUYG LPG G XYUG kG G G G

(5)

SGGGGTG GGoihsGGG

GlUGGGGUG G

G r

r aG oihsSG{wsSG{hsSGmjzSGljoSGTG UG

G

(6)

GG

zGaGYWX^TYYX[^G

G

(7)

GG

jG

hG½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½GXG

jG½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½G[G

sGGG½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½G]G

sGG½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½G_G

XUGpG½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½G`G

YUGtGGG½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½GX[G

YUGXUGjGGG½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½GX[G

YUGYUGwGG½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½GX[G

YUGZUGoGGGG½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½GX_G

YUG[UG~GGG½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½GYXG

YUG\UGwGGGG½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½GYXG

ZUGyGGk½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½GYZG

ZUGXUGjGGGXaGjhGGG½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½GYZG

ZUGYUGjGGGYaGoihsGGjhG½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½GZWG

ZUGZUGjGGGXGGGYaGoihsGGG½½½½½½½½½½½½½½½GZXG

[UGjG½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½GZ_G

(8)

yG½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½GZ`G

ῃⶎ㽞⪳G½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½G[WG

G

(9)

G

s

sGGG

mGXUG G w TG GG G¡ G½½½½½½½½½½½½½½½½½½½½½½½½½½½½½GXYG

mGYUGG G zGGG¡ G GGoihsGGG½½½½½½½½GXZG

mGZUG G zkzTwhnlGGG{hsGG{wsGGG½½½½½½½½½½½½½½½½½½½½½½½½½½½½GX`G

mG[UG G zkzTwhnlGGGGYGGG½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½GYWG

mG\UG G iGGsT GGy{hsGGz{hsGG

G½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½GY]G

mG]UG G iGGGGsT GGj{wsGGy{hsG

GG½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½GY^G mG^UG G iGGGGj{wsGGy{hsGTG

G½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½GY_G

mG_UG G zkzTwhnlGGGj{wsGMGz{hsGTGG½½½½½½½½½½½½½½½½½½½½GY`G

mG `UG G iG GjhG G mjzG MG ljoG G hG MG wG T

GG½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½GZZG

mG XWUGiG GjhG G mjzG MG ljoG TG G G

GGGG½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½GZ[G

mG XXUGiG GjhG G yhylG G imjzGMG iljoG

GGGGG½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½GZ\G

(10)

mGXYUG G iGGGGGXGGGYGG

G½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½GZ]G

mG XZUG G zkzTwhnlG G G imjzG MG iljoG G G G j{wsG MG z{hsGTGG½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½GZ^G

G

(11)

G

s

sGGG

{GXUGwGGGGGG G½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½GX]G

{GYUGwGGGG G½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½½GX^G

G

(12)

GG XU pG

To ¡ G OoihsPG G G G G G G G

G G G G G G G G SG G

GG UXSGYGhSGGGGGGGGGGG

GGUZSG[GpGGG GGGG

oihsGGSGGG GGGGUG OPGyT{GGGGGGGGGG

GGGGGGG¡TGGG

G ¡G G G G G G G G G G G

GGoihsGGG U\OPGkGGG G¡G G

GGGGGGGGU]G

oSG G G G G G G G G

G G G G G G G G G

G G G G G G G G G G G

GGU^GhSG SGGG GG

G G ¡G G G G G G G G G

SG GG GG G GG G G G

GGGGUG_SG`G G

mGGGGSG GGoihsGG GGGG

G G G G ¡ SG G G G TG G

G G G G SG G G G G G

GoihsG GG sT GGTG UGXWSG XXG tG

(13)

SG GG GO{hsPGGGGsT GG

TGSGGGm TjhG GOmjzPGGT G jhG G h{wG G jhSG G G G G G ȻSG ȼG G G

GGT GjhG GoihsG G GjhG VG OljoPUGXXSGXYG

qG uG G SG G G G G GjhG GoihsG

G mjzG G ljoG TGlUG G G G G G WU[^G G ]U[XG tV^SG G G G G G G hG

GOhkoPGGG G GGUXZG hG G G ¡ G G G G h{wG G jhG G G

G G G SG G G G ¡ G G

G G G G G G G G G

G{ G GGiG G O{hkvGMG iwhkPGG_U\^GtVGGoihsGGjhUGX[GhSGz GqGGG

G G WUX[G t^GGoihsG G XUXG tG G sT G G mjzG G ljoG G iG G inyXG OimjzG MG iljoPG G {hsG G yGGOy{hsPGTGlUUGX\G G

oSG G G G G G G G G G G

G G SG G G G G G G

GGGGGUG G

pG G SG G G G G G G G GlUUG mGGGXSG GG GGjGGOj{wsPGG

G G G G zG G Oz{hsPG G

(14)

G G GlUUG {G G G G \t^GG G

GWU_GtGGjhGGXYGO_GLPUG G

mG G G YSG ¡ G G G OimjzG MG iljoPG G

G G O{hkvG MG iwhkPG G G G G

GGG¡ GGGUGlGGGG

G G GjhG GoihsSG G G ¡ G G

GGG[U[GtGGoihsGG\GtGGjhSGGG¡ G

G UG mG ¡SG G G G G

G G G G G G G G G

G G G G G G G O[G tVPSG G G G

GGUG G

m SG G XG G G YG G G G G SG G

GGGGUG{GG GGGWUX\GtG

GoihsGG\GtGGGOZLPUGkGGGGSGGG

GTG GGoihsGGGGGGUG

G G G G G G G G

(15)

G G G G G

G G

G

mGXUGw TG GG G¡ UG G

G

(16)

GG

G

G G

G

mGYUGGzGGG¡ G GGoihsGGUG

G

(17)

GG

YUGtGGG

YUXUGjGGG G

hG SG G G SG jhSG oihsSG T ¡ G G OoihvsPSGT ¡G OoihPSG G SG G G OktzvPSG SG SG TT ȼ TkT G Opw{nPSG

GGzThGOzUGsSGtvSG|zhPUGiGSGsG iGOsiPGSGGGGO{iPGGGGGikGkG OmG sSG uqSG |zhPUG hG G G G G G G G G

UG

G

YUGYUGwGG

mG G G G G XSG ojppG G G G ¡G G

GG GGjUGGOj{wsPGG GG

GrpGMGiopGG G G wUG ǯG G G rG SG zSG zG rUG {G G G G G G l{kTXG G

G G GG G X]G Gko\ȻG G G UG { G G G GzUG G GyUG G Oz{hsG G y{hsSG PGGG¡GG ¡G GiGOzSG rPUGlG{hsGGGGGl{Y[GGlypGGopppUUGmG

G G YSG G jhG G OmjzPG G G jhG VG

GiUG G inyXG G G G G l{XG G G

(18)

iopGGpUX^GhGG GOhkvPGG{UGGG

G G G OwhkPG G iUSG G G G

¡G G ¡G G iG OzSG rPG G G G G

l{kTXGGGGGGGqGuGUGX[G

G

(19)

G

{GXUGwGGGGGG G

Ȁ

ʹͶ

ͳͷ͹ǡ

ȏͳͺȐ

Ǧͳ ͵ʹʹ͹ǡ Novagen

Ǧͳ ͹ǡ Novagen

Ǧͳ ͳͷ͹ǡ Novagen

Ǧʹ ͳ KRIBB

ǦʹC. Freundii

ǦͳC. freundii

ʹͶ ʹͶR. Sphaeroides

ʹͶ ʹͶS. espanaensis

Ǧͳ ƬB. glumae ͳ ȏͳ͹Ȑ

ǦͳT. thermophile

B. Coagulans

ȏͳͶȐ

ͷſ Ǧ80dlacZ M15 (lacZYA-argF) U169 recA1 endA1hsdR17(rk-, mk+) phoAsupE44 -thi-1 gyrA96 relA1

NEB

ͳ͸ͷͷȋ͵Ȍ

ʹͳȋ͵Ȍ

- λ- ilvG- rfb-50 rph-1ȋ͵Ȍ

- ompT lon hsdSB (ǦǦ) gal dcmȋ͵Ȍ

ͳ͸ͷͷȋ͵Ȍ ΔdkgB ΔyeaE Δ(yqhC-dkgA) ΔyahK ΔyjgB ΔendA ΔrecA

[19]

NEB

[20]

(20)

ͳ ʹͳȋ͵Ȍ

ʹ ʹͳȋ͵Ȍ

ʹͳȋ͵ȌʹͶ

ͳ

ʹ

ͳ

ʹ

ͳ

ʹ

ʹͳȋ͵ȌʹͶ

ʹͳȋ͵Ȍ

ʹͳȋ͵Ȍ ǡ ʹͶ

{GYUGwGGGG G

Ǧ ACATATGGCAGATCTCATGAACTACCCTGCCG

Ǧ CAGACTCGAGGGTACCTTATATATAATCAAAC

Ǧ GTTTGATTATATATAAGGTACCCTCGAGTCTG

Ǧ CGGCAGGGTAGTTCATGAGATCTGCCATATGT

(21)

GG

YUGZUGoGGGG

lUG G isYXG OklZPG G G ¡G G G G UG wG kuhG G G G G G G G G G

UG mG G G G SG G G G G G G

G G G G YG sG G siG G G G

G G Z^G ¶jG UG {G TG G G G G

\WG{TiGO{iPGGY\WGsGGGGGGZ^G ¶jGGG

G G G G G G G ]WWG G Ovk]WWPG G WU]TWU_G G pw{nGUG G

{GGGG GGWUXGtGpw{nGGZWG ¶jGGX]GUG{G

GGG¡ GGG GGG[¶jG[[WW̳GGX\G

SGGGTGGGYWGsG{GGOXWWGtSGoG_UWPSGG

G GUG{GGGGG GGGG

G G X]SWWWG G G ZWG G G G G zkzTwhnlG G

G\GG GGGGGMGGGGGG XWW¶jG G \G UG hG SG G G G G XWLG whnlG

SGG GGSGGGGGUGOmUG ZGGmG[PG

G

(22)

G OPG

G

mGZUGzkzTwhnlGGG{hsGG{wsGGUGOPSGy{hsGG z{hsO\\G kG PG G OPSG j{wsO\XG kPG G z{hsG O\\G kPG G

G G isYXOklZPUG taG SG {aG G G G zaG G SG

UG

(23)

G

OPG

G OPG

G

mG[UGzkzTwhnlGGGGYGGUGOPGimjzGO]`GkPGMG iljoGOZWkPGG{hkvGO]^GkPGMGiwhkGOX`GkPGGTGG isYXGOklZPUGtaGSG{aGGGGzaGGSG UG

GG

(24)

GG

YUG[UG~GGG G

jG G G G G G G G XWWG tG {G ojG

G OoG _UWPSG G G G G G G UG {G G G

G G G G XWWG sG G G G G SG G G G

G G G ZWG vk]WWG G G XWG G G YG G UG pG G G XSG

G G G G G G O\G G XWG tPG G G G G

G GGsT GOZGGXWGtPGGXWWtGGGUG pGGGYSG\GtGGjhGGGGGGGGYGGUG

G G G G ZWG ¶jG G YWWG SG G WU\G sG G G

G G G WU\G sG G G G G UG {G

G G G G G G G WUYG ɆG G G G owsjG UG G

G

YUG\UGwGGGG

xG G G G G owsjG s`XWWG G G T

G |}G G G G sG jG Oh SG n SG zG rPG G G ~G G jX_G G O[U]X\WSG \UWtG

G ¡SG ~PUG hG G G G G hG OSG WUXLG {mhPG G

G iG OSG WUXLG {mhPG G G G aG WT\G SG \LG

GiGGaG\TXYGSG\WLGGiGGSGXYTX\GSGG

G\WLGGiaGX\TYWGG\LGGiGOGSGWU^GsVPUGlGG

G G G Y^WG G G G G G SG sT SGT

(25)

¡G OoihPSGoihsG GjhG G ]UYSG YU^SG XWU]SG X_UYG G YXUZG

G UG lG G G G G G G G owsjG

GGGGGGUG G

GG

G

(26)

GG

ZUGyGGkG

ZUGXUGjGGGpaGjhGGG

{ G G G G G G \TG OwswPG G ¡ G

¡G ƀG G G sT SG G G G SG

G G UYXG |G G G G G SG G G

G G G G j{wsG O G G G G jUPG G

G GƀG G G G G G G G G G

sT YXSG YYUG hSG G j{wsGG G G G G G G

G sT G SGjhG SG G G G G

¡G G G UYZTY]UG mG G SG j{wsG

GGGGGXUG G

{G G {hsG G G G G G GlUG G G

G G G G G G G UG pG ZtGG

G SGlUG GG y{hsG G G G G WU\G tG GjhG

GYGtGGjhGGGGGGz{hsGGY[UGOmG\PGiGGG

GSGz{hsGGGGGGXG G

{G GjhG G SG lUGG j{wsG G z{hsG G G G

GGXWWtGGGGGGGXWtGG sT G G G G G G G G {wsG G {hsG

G UG pG XWtG G G G G SG G G

G j{wsG G z{hsG G G G G `U^G G _UYtG G sT

(27)

GGjhSG GGXYUGOmUG]PG{GGGj{wsGG z{hsG G G G G G G G G G G

G G XWWtG G ǯG G G G G {hsG G G

G {wsG G G G G G G G G G G

UG

w SG G j{wsG G z{hsG G G G G G G G

GGGG GG]WWGGOvk]WWPGGGGGX\UG oSG GWU^GtGGjhGGGSGGGGGGsT

G G G UG mG G SG G G G G G G

G G G G UG iG G G j{wsG

G z{hsGG TG G G SGG G G G G

GGGGXWtGGSGYWtGG GGXWWtGUG {GGGGGsT SGGWU\GtGGjhGGGO\GLPG

G XYUG OmUG]PG jG G G G G G {hsG G G G {wsGGGzkzTwhnlGOmG^PSGG GGGG{wsGG{hsG

GGGGjhGG UG G

pGGGGGGGGj{wsGGGojppGGG

G G G G G G G G G G G G

GO\WW¥^WWPGTGj{wsGGz{hsGGGGGG

GGpw{nUGmGGGG SGGj{wsGGTG

GGl{kTXGGGTGGl{Y[z{hsGGG

UG {G G G G G G G G GG G

ojppj{wsG G UG OmG ]PG ~G G j{wsG MG z{hsG G T

(28)

G G pw{nG G SG G G G G G G

G G G G ¡ G G SG G G zkzTwhnlG OmG `PG

G G G GjhG G G G G G G G G

ojppj{wsGGO_GLPUG{GGG GG GG{hsG

GG{wsUGmGGG GGGGGG

UG G

G

(29)

G

mG\UGiGGsT GGy{hsGGz{hsGG

UGyGaGzGSGZtG GOktzvGXWLPbG }SGYsbG{SGZW¶jbGjG SGisYXGOklZPGGl{Y[y{hsGG

l{Y[z{hsUjGvk]WWSGZWbG{GSGXWWGtbGoSG_UWUG G

0 1 2 3

0 5 10 15 20 25

pCA(mM)

Time(h) RsTAL

SeTAL

(30)

G OPG

G

mG ]UG iG G G G sT G G j{wsG G y{hsG

GUGyGaGzGSGXWtGGG

G OktzvG XWLPSG XWWtG G G YWtG G G {wsbG }SG YsbG {SG ZW ¶ jbG jG SG isYXG OklZPG G ojppj{wsG G

l{Y[z{hsG SGjGvk]WWSGZWbG{GSGXWWGtbGoSG_UWUG

0 2 4 6 8 10

0 2 4 6 8 10 12

L-tyrosine(mM)

Time(h)

0 2 4 6 8 10

0 2 4 6 8 10 12

pCA (mM)

Time(h)

(31)

G OPG

G

mG^UGiGGGGj{wsGMGz{hsGTGUG yG aG zG SG G XWtSG G YWtSG

GXWWtbG}SGYGsbG{SGZW¶jbGjG SGisYXGOklZPGG OPG ojppj{wsG MG l{Y[z{hsG G OPG PG l{j{wsG MG l{Y[z{hsSG jGvk]WWSGZWbG{GSGXWWGtbGoSG_UWUG

0 2 4 6 8 10 12

L-tyrosine and pCA (mM)

Time (h) L-tyrosine pCA

0 2 4 6 8 10

0 2 4 6 8 10 12

L-tyrosine and pCA (mM)

Time (h) L-tyrosine pCA

(32)

G

OPG

G OPG

G

mG _UG zkzTwhnlG G G j{wsG MG z{hsG TG UG j{wsO\XG

kPG G z{hsG O\\G kPG G TG G isYXOklZPG G OPG G

ojppj{wsG MG l{Y[z{hsG G OPG l{kj{wsG MG l{Y[z{hsUG taG

SG{aGGGGzaGGSG UG G

(33)

GG

ZUGYUGjGGGYaGoihsGGjhG

pG G G YSG G SG G G G G ¡ G G OimjzG MG iljoPG G G O{hkvG MG iwhkPG ¡ G G

G G lUSG G G G G G jhG G

GUG G

~GlUG G {hkvG MG iwhkSG XUXG tG GoihsG G G G XYG

G G ZU]G tG G T G Ooz{PG G G G

GGiwhkUGpGGGimjzGMGiljoGTGSG [U[GtGG

oihsGGUGOmG^GGmG_PUGw SGGGG¡ G

G GSGX[]GtGGoihsGGX]WGtGGjhGG G

GGGGGGUG~GGGGGGG

SG G imjzMG iljoG G G G G G G G G {hkvMG iwhkUG w SG G G G G G G G

G G G G G G G G G UG G hSGGG GGO SGGG[WLPGGG

G G G \W ¶ jG G ZW ¶ jG G G X[SG imjzG MG iljoG G G G G G {hkvMG iwhkG UG {SGimjzGMGiljoGGGGGUG G

iG G G G G imjzG G h{wG G jhSG G G

G G G G G imjzMG iljoG G G G

G G G G TUG hG SG G G G G

GGXU_tVGGZU^tVGGWUY\LGGSGGGG

(34)

GT ¡G OoihsjvsPG G G G G G XUXG tG G XU]G

tUG{GGGGGGGGGGG G h{wG G jhG G G uhkoG G G G G G G hG GOhkoPUY^G

{G G G G G G G G SG G G G G

G hkoG G UG y G h G tUG rG G G G lUG tnX]\\G G G G G G G OyhylPG G

G G G hkoG G G TG G OhryPG G

UYWG hG G G G SG yhylG G G G G

GoihsUG

imjzG MG iljoG G l{G G G G G yhylG

GGGGGGGjhGGGGGUG {GGGG G[tVGGGGGGGWUY\GGWU\LG

SG YU`tVG G G G G UG {G G G oihsG G

oihsjvsG G G XYG G G G O[UZ¥[U\G tG GoihsG G WU^¥WU`tGGoihsjvsPUGhGG GGGGGG

GG GGGyhylGGimjzGMGiljoSGG

GGGGGGGXUG G G G G G G G G

G ZZUGZUGjGGGXGGGYaGoihsGGG

G hG G XG G G G G G SG G G G G G

G G G XG G G YG G G G G G G

GGGGYGGGGUGnGG

(35)

G XG G G YG G TG G yhylG G G G

UG G

pGGG\tGGSGGGGGZU_GtGGsT SG

GWUW]GtGGoihsGGXUX]GtGGjhGGGGXYUGiGG

GGGGGGSGGGGGimjzGGiljoG

G G SG G G G imjzG MG iljoG G

G UG OmUG XZPG tG G G G G

G G G G G G G G G UG kG G G G

SGGGGTG GGoihsGGG

GlUGGGGUG G G GG G GG

G

(36)

G

G G

mG `UG iG GjhG G mjzG MG ljoG G hG MG wG T

G UG yG aG zG SG \G tGjhbG }SGXWGsGGXWWGsGbG{SGZW¶jbGjG SGisYXGOklZPGG

l{GmjzTljoGGhkvTwhkSG bGjGvk]WWSGZWbG{GSGXWWG

tbGoSG_UWUG G

R%#R*$#.R*$#.%1*1.CPFR*56O/

6KOGJ

)(S&$ $3S&$ %J)&6%J(&+

7W$'2%F3$' )(S+%$/&2+2/ $3S+%$/&2+2/

%/3DG$GRS+VW\UHQH

(37)

G

G G

GG

G

mG XWUGiG GjhG G mjzG MG ljoG TG G G

G G G UG yG aG zG SG \G tG

jhbG }SG XWG sG G XWWG sG bG {SG ZW¶jbG jG SG isYXG OklZPG

G l{G mjzTljobG jG vk]WWSG ZWbG {G SG XWWG tbG oSG _UWbG

G G G G G G G WG G WU\LG OVPG G _WLG

GUG G G

R%#R*$#.CPFR*$#.%1*1.O/

6KOGJ

)(S&$ )(JOXFRVHS&$

)(JOXFRVHS&$ )(S+%$/

)(JOXFRVHS+%$/ )(JOXFRVHS+%$/

)(S+%$/&2+2/ )(JOXFRVHS+%$/&2+2/

)(JOXFRVHS+%$/&2+2/

(38)

G

G G

mGXXUGiGGjhGGyhylGGimjzGMGiljoG

GGGGUGyGaGzGSG\GtG

jhbG}SGXWGsGGXWWGsGbG{SGZW¶jbGjG SGisYXGOklZPG

Gl{GmjzTljobGjGvk]WWSGZWbG{GSGXWWGtbGoSG_UWbG

GGGGGGGWGGWU\LGOVPGG_WLG

GUG G

R%#R*$#.CPFR*$#.%1*1.O/

6KOGJ

5$5()(S&$ 5$5()(JOXFRVHS&$

5$5()(JOXFRVHS&$ 5$5()(S+%$/

5$5()(JOXFRVHS+%$/ 5$5()(JOXFRVHS+%$/

5$5()(S+%$/&2+2/ 5$5()(JOXFRVHS+%$/&2+2/

5$5()(JOXFRVHS+%$/&2+2/

(39)

G

G G G

mGXYUGiGGGGGXGGGYGG

UG yG aG zG SG \tG G SG G

^U\tSG G XWWtSG G WU\LG VSG G lG \LG VbG }SG XWG

sbG {SG ZW¶jbG jG SG yhylG G ojppj{wsSG l{Y[y{hsG

yzmGmjzTljoGjGvk]WWSGZWbG{GSGXWWGtbGoSG_UWUG G

.V[TQUKPGR%#R*$#.CPFR*$#.%1*1.O/

6KOGJ

/W\URVLQH S&$ S+%$/ S+%$/&2/

(40)

G G

G

G G

G

mG XZUG zkzTwhnlG G G imjzG MG iljoG G G G j{wsG MG z{hsGTGUGimjzGO]`GkPGMGiljoGOZWkPGGj{wsGO\XG

kPGMGz{hsGO\\GkPGGTGGisYXGOklZPUGtaGSG{aGG

GGzaGGSG UG

GG

(41)

GG

[UGjUG

T ¡ G OoihsPG G G G G G

G G G SG SG G G G G G G

UG {G GoihsG G G G G G SG G

GG GGGGGlUUG G

pG G G XSG G G G O{wsPG GjG G G

G G G O{hsPG G zG G G

G G GlUG UG {G G G G

G G G zkzTwhnlG G G G G \G tG G

GGGWU_GtGGTGGOjhPGGXYGO_GLPUG G

pG G G YSG G jhG G OmjzPG G G jhG

VG G G G G G G G

G UG {G [U\G tG GoihsG G G G \G tG GjhG G

GGGG[GtVGGGUG

m SGGGXGGGYGGSGGGGWUW]G

tG GoihsG G \G tG G G OXUYG LPG G XYUG tG G

GGGGGGGGGGGUG kG G G G SG G G G TG G G

oihsGGGGlUGGGGUG G

G

(42)

GG

yG

1. Torii, S., et al., Regiospecific electroacetoxylation of 4-methylphenyl acetate to form 4-acetoxybenzyl acetate. A significant procedure for vanillin synthesis involving novel etherification methods of aryl bromides. The Journal of Organic Chemistry, 1979. 44(19): p. 3305-3310.

2. Barton, B., et al., Practical Process for the Air Oxidation of Cresols: Part A.

Mechanistic Investigations. Organic Process Research & Development, 2005.

9(1): p. 62-69.

3. Mulabagal, V., et al., Health-Beneficial Phenolic Aldehyde in Antigonon leptopus Tea. Evid Based Complement Alternat Med, 2011. 2011: p. 601249.

4. Park, S., D.S. Kim, and S. Kang, Gastrodia elata Blume water extracts improve insulin resistance by decreasing body fat in diet-induced obese rats: vanillin and 4-hydroxybenzaldehyde are the bioactive candidates. Eur J Nutr, 2011. 50(2): p.

107-18.

5. Hirao, K., M. Ikegame, and O. Yonemitsu, Photo-Reimer-Tiemann reaction of phenols, anilines and indolines. Tetrahedron, 1974. 30(15): p. 2301-2305.

6. Galstyan, A.G., A.A. Sedykh, and G.A. Galstyan, Kinetics and mechanism of the catalytic reaction between ozone and para-cresol in acetic anhydride. Kinetics and Catalysis, 2008. 49(2): p. 186-190.

7. Kshirsagar, V.S., et al., Heterogeneous Cobalt−Saponite Catalyst for Liquid Phase Air Oxidation of p-Cresol. Industrial & Engineering Chemistry Research, 2009.

48(21): p. 9423-9427.

8. Wang, F., et al., Copper and manganese: two concordant partners in the catalytic oxidation of p-cresol to p-hydroxybenzaldehyde. Chemical Communications, 2003(10): p. 1172-1173.

9. Wang, F., et al., Oxidation of p-Cresol to p-Hydroxybenzaldehyde with Molecular Oxygen in the Presence of CuMn-Oxide Heterogeneous Catalyst. Advanced Synthesis & Catalysis, 2004. 346(6): p. 633-638.

10. Mayer, M.J., et al., Rerouting the plant phenylpropanoid pathway by expression of a novel bacterial enoyl-CoA hydratase/lyase enzyme function. Plant Cell, 2001.

13(7): p. 1669-82.

11. Kang, S.Y., et al., Artificial biosynthesis of phenylpropanoic acids in a tyrosine overproducing Escherichia coli strain. Microb Cell Fact, 2012. 11: p. 153.

12. Ni, J., et al., Mimicking a natural pathway for de novo biosynthesis: natural vanillin production from accessible carbon sources. Sci Rep, 2015. 5: p. 13670.

13. Ni, J., et al., Temperature-Directed Biocatalysis for the Sustainable Production of Aromatic Aldehydes or Alcohols. Angew Chem Int Ed Engl, 2018. 57(5): p. 1214- 1217.

14. Ni, J., et al., A Coenzyme-Free Biocatalyst for the Value-Added Utilization of Lignin-Derived Aromatics. Journal of the American Chemical Society, 2018.

(43)

15. Jang, S., et al., FCS and ECH dependent production of phenolic aldehyde and melanin pigment from l-tyrosine in Escherichia coli. Enzyme Microb Technol, 2018. 112: p. 59-64.

16. Quan, J. and J. Tian, Circular polymerase extension cloning for high-throughput cloning of complex and combinatorial DNA libraries. Nature Protocols, 2011. 6: p. 242.

17. Jung, D.H., et al., Production of p-hydroxybenzoic acid from p-coumaric acid by Burkholderia glumae BGR1. Biotechnol Bioeng, 2016. 113(7): p. 1493-503.

18. Jung, E., et al., Production of ω-hydroxy palmitic acid using CYP153A35 and comparison of cytochrome P450 electron transfer system in vivo. Applied Microbiology and Biotechnology, 2016. 100(24): p. 10375-10384.

19. Tseng, H.C., et al., Metabolic engineering of Escherichia coli for enhanced production of (R)- and (S)-3-hydroxybutyrate. Appl Environ Microbiol, 2009.

75(10): p. 3137-45.

20. Kunjapur, A.M., Y. Tarasova, and K.L. Prather, Synthesis and accumulation of aromatic aldehydes in an engineered strain of Escherichia coli. J Am Chem Soc, 2014. 136(33): p. 11644-54.

21. Phillips, R.S., Reactions of O-acyl-L-serines with tryptophanase, tyrosine phenol- lyase, and tryptophan synthase. Arch Biochem Biophys, 1987. 256(1): p. 302-10.

22. Faleev, N.G., et al., Interaction of tyrosine phenol-lyase with phosphoroorganic analogues of substrate amino acids. Eur J Biochem, 2000. 267(23): p. 6897-902.

23. Seisser, B., et al., Cutting Long Syntheses Short: Access to Non-Natural Tyrosine Derivatives Employing an Engineered Tyrosine Phenol Lyase. Advanced

Synthesis & Catalysis, 2010. 352(4): p. 731-736.

24. Busto, E., et al., Systems biocatalysis: para-alkenylation of unprotected phenols.

Catalysis Science & Technology, 2016. 6(22): p. 8098-8103.

25. Busto, E., R.C. Simon, and W. Kroutil, Vinylation of Unprotected Phenols Using a Biocatalytic System. Angewandte Chemie International Edition, 2015. 54(37): p.

10899-10902.

26. Payer, S.E., et al., Multienzyme One-Pot Cascade for the Stereoselective Hydroxyethyl Functionalization of Substituted Phenols. Organic Letters, 2018.

20(17): p. 5139-5143.

27. Lee, W.H., et al., Engineering of NADPH regenerators in Escherichia coli for enhanced biotransformation. Appl Microbiol Biotechnol, 2013. 97(7): p. 2761- 72.

G G G G G G G

(44)

G

ῃ

ῃⶎ㽞⪳G G

䕢⧒T䞮㧊✲⪳㔲⻺㯞㞢◆䞮㧊✲⓪G 䟻㑮SG 㦮㟓䛞SG 㞷㩫G ⹥G 㔳䛞G ㎇⿚ὒG ṯ㦖G

┺㟧䞲G 㣿☚㦮G ┺₆⓻G 㭧Ṛ㼊⪲㖾SG 㧊⯒G 㩲㫆䞮₆G 㥚䞲G 䢪䞯G 䞿㎇G ἓ⪲ṖG 㧮G 䢫Ⱃ♮㠞㰖ⰢSG ㌗╖㩗㦒⪲G 㠊⩺㤊G ἶ㡾G ἶ㞫㦮G 㫆ỊG ⹥G ⹮㦧㌗G ⍹㠊㭒⓪G ὒ⨟㦮G 㡒₆㦮G 㩲Ệ⓪G 㞚㰗G ⶎ㩲⪲G ⋾㞚㧞┺UG 㧊⩂䞲G 㧊㥶⪲SG sT䌖㧊⪲㔶ὒG 䕢⧒T 䈶Ⱎ⩞㧊䔎⪲⿖䎆G 㨂㫆䞿G ╖㧻‶㦚G 㧊㣿䞲G ㎇Ὃ㩗㧎G ㌳䞿㎇G ἓ⪲ṖG ⽊☚♮ἶG 㧞┺UG

⁎⩂⋮G ㌗╖㩗㦒⪲G ゚㕒G 㩚ῂ㼊㦮G ㌂㣿㦖G ⽊┺G 㩖⪊䞮ⳆG 㩧⁒㎇㧊G ⏨㦖G 㩚ῂ㼊⯒G

㌂㣿䞮⓪G ㌳䞿㎇㦮G 䞚㣪㎇㦚G 㩲Ὃ䞲┺UG

⽎G 㡆ῂ㠦㍲⓪G 䗮⏖⪲⿖䎆G 䕢⧒T䞮㧊✲⪳㔲⻺㯞㞢◆䞮㧊✲⯒G ㌳㌆䞮₆G 㥚䟊G ⚦G Ṳ㦮G ⳾✞㦚G ṗṗG ╖㧻‶㠦㍲G 㩗㣿䞮㡂G 䞿㼺┺UG ⳾✞ X 㠦㍲GjUG G 㥶⧮㦮G

G T G O{wsP㢖GzUG G 㥶⧮㦮G G T G O{hsPṖG ṗṗG lU 㠦㍲G 㧊䡫G 㩗㦒⪲G ⹲䡚♮㠞┺UG ⹲䡚ὒG ⹮㦧㎇㦖G zkzT whnl 㢖G ㎎䙂G ㌳㩚䢮㦚G 䐋䟊G 䢫㧎䟞㦒ⳆSG XWG t 㦮G 䗮⏖㧊G XYG 㔲ṚG ☯㞞G WU_G

t 㦮G 䕢⧒T䈶Ⱎ⩞㧊䔎⪲G 㩚䢮♮㠞┺G O㩚䢮㥾G _G LPUG ⳾✞G Y 㠦㍲⓪G iUG 㥶⧮㦮G G G G OmjzP㢖G G G VG OljoP⯒G 㧊䡫G 㩗㦒⪲G ⹲䡚䞮㡖┺UG \G tG 㦮G 䕢⧒⹿䟻㫇G 㞢◆䞮㧊✲㦮G 䢮㤦㧊G Ṧ㏢♲G ‶㭒⯒G

☚㧛䞮ἶG 䙂☚╏㦚G ⹮㦧㌗㠦G ⍹㠊㭢㦒⪲㖾SG XYG 㔲ṚG ☯㞞G \G t 㦮G 䕢⧒G 䈶Ⱎ⩞㧊䔎⪲⿖䎆G [U[G t 㦮G 䕢⧒䧞✲⪳㔲⻺㯞㞢◆䧞✲⯒G 㠑㦚G 㑮G 㧞㠞┺UG O㩚䢮㥾 `WGLPG

G 㾲㫛㩗㦒⪲G 䞮⋮㦮G ㎎䙂㠦㍲G ⳾✞G X ὒG ⳾✞G Y ⯒G ῂ㎇䞮⓪G 㥶㩚㧦⯒G ⹲䡚䞮㡖ἶSG

㧊G ㎎䙂⯒G 䐋䟊 XYG 㔲ṚG ☯㞞G \G t 㦮G 䗮⏖㧊 WUW]G t 㦮G 䕢⧒T

䧞✲⪳㔲⻺㯞㞢◆䧞✲⪲G 㩚䢮♶G 㑮G 㧞㠞┺UG ⌄㦖G 㩚䢮㥾㠦☚G ⿞ῂ䞮ἶSG 㧊G ἆὒ⓪G

㻮㦢㦒⪲GlU 㦮G 䗮⏖⪲⿖䎆G 䕢⧒T䧞✲⪳㔲⻺㯞㞢◆䧞✲㦮G ㌳㩚䢮㦚G ⽊☚䞮⓪◆G

⁎G 㦮㦮ṖG 㧞┺UG

㭒㣪㠊aG 䕢⧒T䧞✲⪳㔲⻺㯞㞢◆䧞✲SG ㌳㩚䢮UG G

䞯⻞aGYWX^TYYX[^G

이용자는 아래의 조건을 따르는 경우에 한하여 자유롭게

ᙽ㻡⪥⨴㻡れᬄⓀ#

#

w

wGG  To  ¡ GGwG|G lG lGG

㨂㫆䞿G ╖㧻‶㦚G 㧊㣿䞲G 䗮⏖⪲⿖䎆G G 䕢⧒T䞮㧊✲⪳㔲⻺㯞㞢◆䞮㧊✲㦮G ㌳㌆G

GG

jG

s

sGGG

s

sGGG

ῃ

ῃⶎ㽞⪳G G

wGG To ¡ GGwG|G lG lGG

jG

sGGG

sGGG