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黃花蒿中青蒿素生物合成相關(guān)轉(zhuǎn)錄因子研究進(jìn)展

2021-03-16 15:38高曉悅陳萬(wàn)生譚何新
中草藥 2021年6期
關(guān)鍵詞:青蒿性腺青蒿素

李 琦,高曉悅,陳萬(wàn)生,譚何新

黃花蒿中青蒿素生物合成相關(guān)轉(zhuǎn)錄因子研究進(jìn)展

李 琦,高曉悅,陳萬(wàn)生,譚何新*

海軍軍醫(yī)大學(xué)藥學(xué)院,上海 200433

以青蒿素為基礎(chǔ)的聯(lián)合療法是瘧疾的首選治療方案,而藥用植物黃花蒿是青蒿素的唯一天然來(lái)源,也是目前最主要的青蒿素來(lái)源,因此培育高產(chǎn)青蒿素的黃花蒿一直是國(guó)際研究熱點(diǎn)。青蒿素是黃花蒿的次生代謝產(chǎn)物,在植物的次生代謝物合成過(guò)程中,關(guān)鍵的轉(zhuǎn)錄因子可以調(diào)節(jié)代謝途徑中某個(gè)或多個(gè)基因的表達(dá),從而調(diào)節(jié)代謝流的方向和速度,決定著代謝物的產(chǎn)量,因此關(guān)鍵轉(zhuǎn)錄因子的表達(dá)對(duì)于青蒿素的合成非常重要,通過(guò)干預(yù)轉(zhuǎn)錄因子的表達(dá)也是提高青蒿素產(chǎn)量的重要手段。綜述了黃花蒿中已研究的轉(zhuǎn)錄因子功能及調(diào)控機(jī)制,特別是對(duì)篩選獲得轉(zhuǎn)錄因子基因的方法進(jìn)行總結(jié),以期為揭示青蒿素合成調(diào)控網(wǎng)絡(luò)奠定基礎(chǔ)。

黃花蒿;青蒿素;轉(zhuǎn)錄因子;代謝調(diào)控;次生代謝物

據(jù)世界衛(wèi)生組織(World Health Organization,WHO)報(bào)道,2018年全球共有2.28億瘧疾病例報(bào)告,其中40.5萬(wàn)例死亡,2010~2018年瘧疾的發(fā)病率及死亡率均呈下降趨勢(shì),特別是重災(zāi)區(qū)非洲的瘧疾死亡率下降尤為明顯,這很大程度上歸功于以青蒿素為基礎(chǔ)的聯(lián)合療法(artemisinin-based combination therapy,ACT)的應(yīng)用,目前ACT仍為WHO推薦的瘧疾首選治療方案[1]。如何高效獲得青蒿素一直是國(guó)際研究熱點(diǎn),化學(xué)合成方面,早在1983年瑞士科學(xué)家Schmid和Hofheinz就提出了青蒿素的化學(xué)全合成方案,但反應(yīng)步驟多、條件苛刻、試劑昂貴、得率低,后續(xù)提出的化學(xué)合成方案均存在類似問(wèn)題[2]。合成生物學(xué)方面,Keasling團(tuán)隊(duì)在青蒿酸生物合成方面的研究堪稱合成生物學(xué)的典范,然而由于青蒿素的最終合成需要特殊的油性氧化環(huán)境,在酵母中難以實(shí)現(xiàn),因此目前較為成熟的方法仍為生物合成青蒿酸[3]。Paddon等[4]提出以青蒿酸為原料的化學(xué)半合成方案,最終青蒿素的得率為40%~45%,且存在分離純化困難的問(wèn)題。目前最為經(jīng)濟(jì)的獲得青蒿素的方法仍為從植物中提取,而青蒿素在植株中的含量較低,僅占干質(zhì)量的0.1%~1%[5],隨著青蒿素臨床治療應(yīng)用的開(kāi)發(fā),其市場(chǎng)需求會(huì)進(jìn)一步加大,因此需要提高青蒿素的產(chǎn)量。

青蒿素是來(lái)源于藥用植物黃花蒿L(fēng).的次生代謝產(chǎn)物,其生物合成途徑屬于類異戊二烯途徑(圖1),由質(zhì)體中的異戊二烯(meth-ylerythritol phosphate,MEP)途徑提供1個(gè)異戊烯基焦磷酸(isopentenyl phosphate,IPP)和細(xì)胞質(zhì)中的甲羥戊酸(mevalonic acid,MVA)途徑提供1個(gè)二甲基烯丙基焦磷酸(dimethylallyl diphosphate,DMAPP)和IPP,然后1份DMAPP和2份IPP在法尼基焦磷酸合成酶(farnesyl diphosphate synthase,F(xiàn)PS)的催化下聚合生成法尼基焦磷酸(farnesyl diphosphate,F(xiàn)PP)[6-7]。從FPP開(kāi)始進(jìn)入青蒿素合成特異的下游代謝途徑,F(xiàn)PP經(jīng)紫穗槐二烯合成酶(amorpha-4,11-diene synthase,ADS)催化生成紫穗槐二烯[8];紫穗槐二烯經(jīng)過(guò)3步由細(xì)胞色素P450單氧化酶(Cytochrome P450 monooxygenase,CYP71AV1)催化的反應(yīng),分別形成青蒿醇,青蒿醛和青蒿酸[9-11]。青蒿醛可在青蒿醛雙鍵還原酶[artemisinic aldehyde delta-11(13)reductase,DBR2][12]和醛脫氫酶1(aldehyde dehydrogenase 1,ALDH1)[13]的催化下先轉(zhuǎn)化成二氫青蒿醛(dihydroartemisinic aldehyde),然后生成青蒿素的直接前體二氫青蒿酸(dihydroartemisinic acid,DHAA)。同時(shí),青蒿醛也會(huì)在CYP71AV1 和 ALDH1的催化下生成青蒿酸(artemisinic acid)[11, 13];從DHAA到青蒿素(artemisinin),以及青蒿酸到青蒿素B(arteannuin B)的轉(zhuǎn)化目前認(rèn)為是非酶促的光氧化反應(yīng)[14-17]。在植物的次生代謝過(guò)程中,轉(zhuǎn)錄因子可以調(diào)節(jié)代謝途徑中的一系列基因,對(duì)轉(zhuǎn)錄因子的干預(yù)是一種有效的調(diào)控植物次生代謝產(chǎn)物的方法[18]。本文按照獲得轉(zhuǎn)錄因子基因的不同途徑進(jìn)行分類,綜述了黃花蒿中轉(zhuǎn)錄因子的研究進(jìn)展。

圖1 青蒿素生物合成途徑

1 激素響應(yīng)轉(zhuǎn)錄因子

1.1 脫落酸(abscisic acid,ABA)對(duì)黃花蒿bZip1基因(AabZip1)的影響

ABA的處理能提高青蒿素積累[19],在模式植物擬南芥中A類bZip家族轉(zhuǎn)錄因子響應(yīng)ABA信號(hào)[20]。Zhang等[21]通過(guò)bZip家族保守結(jié)構(gòu)域查詢黃花蒿公共cDNA數(shù)據(jù)庫(kù),得到145個(gè)候選基因,其中64個(gè)能在分泌性腺毛中表達(dá),通過(guò)與擬南芥A類bZip轉(zhuǎn)錄因子基因構(gòu)建系統(tǒng)進(jìn)化樹(shù),篩選得到6個(gè)黃花蒿A類bZip轉(zhuǎn)錄因子基因,再通過(guò)在煙草中進(jìn)行雙熒光素酶實(shí)驗(yàn)驗(yàn)證能否激活及的表達(dá),獲得目的基因。后續(xù)實(shí)驗(yàn)表明受ABA、干旱、高鹽脅迫的誘導(dǎo)表達(dá),AabZip1通過(guò)激活和的表達(dá)影響青蒿素的合成,其過(guò)表達(dá)可使青蒿素和二氫青蒿酸含量分別提高40%~60%、41%~53%。

1.2 茉莉酸(jasmonicacid,JA)和茉莉酸甲酯(methyl jasmonate,MeJA)

1.2.1 黃花蒿基因() bHLH家族的MYC2類轉(zhuǎn)錄因子被認(rèn)為是參與JA信號(hào)通路的核心因子[22-23]。Shen等[24]在黃花蒿葉片cDNA文庫(kù)中發(fā)現(xiàn)5個(gè)MYC2類轉(zhuǎn)錄因子片段序列,其中1條與MeJA處理后的擬南芥中的MYC2基因的表達(dá)模式相同,用RACE方法獲得其全長(zhǎng)序列,命名為。后續(xù)研究表明過(guò)表達(dá)能提高和的轉(zhuǎn)錄水平,可使青蒿素和二氫青蒿酸含量分別提高23%~55%、17%~217%。

1.2.2 黃花蒿基因() JA能促進(jìn)黃花蒿分泌性腺毛起始[25],JAZ蛋白是茉莉酸信號(hào)通路的重要調(diào)控因子,在擬南芥中能影響腺毛的起始[26],Yan等[27]用AaJAZ8篩選黃花蒿幼葉cDNA文庫(kù),發(fā)現(xiàn)1個(gè)HDZip家族轉(zhuǎn)錄因子AaHD1能與AaJAZ8相互作用,且受茉莉酸的正調(diào)控。后續(xù)研究表明過(guò)表達(dá)能在不影響植物生長(zhǎng)的情況下增加成熟葉片表面分泌性腺毛密度,使青蒿素含量提高50%。

1.2.3 黃花蒿基因(、) AP2/ERF家族轉(zhuǎn)錄因子參與植物激素信號(hào)響應(yīng)及次生代謝[28]。Yu等[29]通過(guò)在分泌性腺毛cDNA文庫(kù)中查找AP2/ERF家族轉(zhuǎn)錄因子保守結(jié)構(gòu)域,獲得7個(gè)片段序列,其中2個(gè)符合在花中表達(dá)、且受MeJA誘導(dǎo)的表達(dá)模式,用RACE的方法獲得這2條序列的全長(zhǎng),即和。后續(xù)研究表明AaERF1、AaERF2均能激活的表達(dá),過(guò)表達(dá)可使青蒿素和青蒿酸的含量提高19%~67%、11%~76%,過(guò)表達(dá)為24%~51%、17%~121%,且基因可能通過(guò)JA和乙烯信號(hào)通路,激活部分防御基因,提高黃花蒿對(duì)灰霉病菌Pers.的抗性[30]。

1.3 水楊酸(Salicylicacid,SA)對(duì)黃花蒿TGA6基因(AaTGA6)

SA在植物對(duì)病原菌的防御響應(yīng)中起重要作用[31],在擬南芥的SA信號(hào)通路中TGA2、NPR1是重要調(diào)節(jié)因子[32-33]。Lv等[34]分析黃花蒿轉(zhuǎn)錄組數(shù)據(jù),發(fā)現(xiàn)有6條TGA類轉(zhuǎn)錄因子序列,通過(guò)與擬南芥TGA轉(zhuǎn)錄因子基因構(gòu)建系統(tǒng)進(jìn)化樹(shù),同源性最高的為。后續(xù)研究表明的表達(dá)能被AaNPR1增強(qiáng),被AaTGA3抑制,同時(shí)AaTGA6能調(diào)控基因的表達(dá),過(guò)表達(dá)可使青蒿素含量提高90%~120%。

2 通過(guò)分析啟動(dòng)激活元件獲得轉(zhuǎn)錄因子

2.1 黃花蒿WRKY1基因(AaWRKY1)

Han等[35]分析基因的啟動(dòng)子發(fā)現(xiàn)其含有2個(gè)W-box,可能受WRKY家族轉(zhuǎn)錄因子調(diào)控,通過(guò)比對(duì)分泌性腺毛的cDNA文庫(kù),發(fā)現(xiàn)其中有1條轉(zhuǎn)錄因子的片段序列,用RACE方法獲得全長(zhǎng)序列,命名為。后續(xù)研究表明AaWRKY1能提高及其它青蒿素合成途徑基因的表達(dá),且在腺毛中特異的過(guò)表達(dá)比在植物中廣泛的過(guò)表達(dá)能更有效的提高青蒿素的積累。

2.2 黃花蒿MYB1基因(AaMYB1)

Matías-Hernández等[36]發(fā)現(xiàn)多數(shù)青蒿素合成途徑基因啟動(dòng)子區(qū)域均含有MYB家族轉(zhuǎn)錄因子結(jié)合位點(diǎn),推測(cè)有MYB家族轉(zhuǎn)錄因子參與調(diào)控青蒿素生物合成。分析公共黃花蒿分泌性腺毛cDNA文庫(kù),發(fā)現(xiàn)1個(gè)符合R2R3-MYB轉(zhuǎn)錄因子特征的片段,用RACE的方法獲得全長(zhǎng)序列命名為。后續(xù)研究表明,的過(guò)表達(dá)可以提高青蒿素合成途徑基因的表達(dá)水平,增加分泌性腺毛數(shù)量及密度,提高青蒿素的積累。

2.3 黃花蒿bHLH1基因(AabHLH1)

Ji等[37]發(fā)現(xiàn)基因啟動(dòng)子區(qū)域均含有bHLH家族轉(zhuǎn)錄因子結(jié)合的E-box,推測(cè)可能被bHLH家族轉(zhuǎn)錄因子調(diào)控,在黃花蒿分泌性腺毛cDNA數(shù)據(jù)庫(kù)中分析發(fā)現(xiàn)3條可能的bHLH家族轉(zhuǎn)錄因子基因片段,用RACE方法能獲得了其中2條基因的全長(zhǎng),酵母單雜交實(shí)驗(yàn)及EMSA實(shí)驗(yàn)證明AabHLH1能與E-box結(jié)合,因此選定為目的基因。后續(xù)研究表明,AabHLH1能結(jié)合的啟動(dòng)子并提高青蒿素合成途徑基因的轉(zhuǎn)錄水平。

2.4 黃花蒿HD8基因(AaHD8)

Yan等[38]分析的啟動(dòng)子發(fā)現(xiàn)含有L1-box,預(yù)測(cè)可能被HD-Zip家族轉(zhuǎn)錄因子結(jié)合,利用酵母單雜交、雙熒光素酶實(shí)驗(yàn)篩選已獲得的HD-Zip IV亞家族轉(zhuǎn)錄因子基因,獲得。后續(xù)研究表明AaHD8能激活的表達(dá),從而起始分泌性腺毛的發(fā)育,另外AaHD8還能與AaMIXTA1相互作用,調(diào)節(jié)腺毛發(fā)育及角質(zhì)層形成。

3 與已知功能基因同源的黃花蒿轉(zhuǎn)錄因子基因

3.1 擬南芥

3.1.1 黃花蒿基因() 擬南芥ORA59能在植物防御中整合JA和乙烯信號(hào)[39]。Lu等[40]通過(guò)擬南芥基因序列在黃花蒿分泌性腺毛cDNA文庫(kù)中查詢,得到1個(gè)同源性最高的片段,用RACE方法獲得其全長(zhǎng)序列,即。后續(xù)研究表明ABA處理、創(chuàng)傷、寒冷能顯著提高的轉(zhuǎn)錄水平,MeJA、乙烯處理也能輕微的誘導(dǎo)表達(dá),從而參與植物抗逆。

3.1.2 黃花蒿基因() MYB家族轉(zhuǎn)錄因子中MIXTA或MIXTA樣轉(zhuǎn)錄因子能控制多種植物的細(xì)胞形態(tài)、腺毛發(fā)育和起始等,如擬南芥AtMYB16和AtMYB106調(diào)控腺毛分枝及表皮細(xì)胞形態(tài)[41]。Shi等[42]以擬南芥已知MYB家族轉(zhuǎn)錄因子序列在黃花蒿各組織的轉(zhuǎn)錄組數(shù)據(jù)庫(kù)中查詢,獲得的序列與擬南芥及其他物種已知的MIXTA或MIXTA樣轉(zhuǎn)錄因子共同構(gòu)建系統(tǒng)進(jìn)化樹(shù),篩選獲得與擬南芥、同源性最高的序列,即。后續(xù)研究表明AaMIXTA1可以調(diào)控分泌性腺毛的數(shù)量和角質(zhì)層的生物合成,過(guò)表達(dá)可以在不影響分泌性腺毛結(jié)構(gòu)的情況下提高青蒿素的積累。

3.1.3 黃花蒿基因() 青蒿素的生物合成量在低溫處理后顯著升高[43-44],而擬南芥中2個(gè)低溫相關(guān)的轉(zhuǎn)錄因子AtICE1和ATICE2均屬于bHLH家族[45-46]。Xiang等[47]以bHLH保守結(jié)構(gòu)域在青蒿基因組數(shù)據(jù)庫(kù)中查詢,得到基因組中205個(gè)結(jié)果、轉(zhuǎn)錄組中122個(gè),按bHLH家族轉(zhuǎn)錄因子特征進(jìn)行分類,其中屬于與青蒿素合成相關(guān)的V家族轉(zhuǎn)錄因子15個(gè),與擬南芥bHLH轉(zhuǎn)錄因子共同構(gòu)建系統(tǒng)進(jìn)化樹(shù),2條序列與擬南芥、同源性最高,其中僅受低溫誘導(dǎo)。后續(xù)研究表明,AabHLH112能調(diào)控的表達(dá),從而提高青蒿素合成途徑基因的轉(zhuǎn)錄水平,過(guò)表達(dá)的株系中青蒿素及二氫青蒿酸含量均顯著上升。

3.2 其他

3.2.1 黃花蒿基因() 長(zhǎng)春花的過(guò)表達(dá)可以增加萜類化合物的積累[48],Lu等[49]以長(zhǎng)春花序列作為查詢序列在黃花蒿葉片cDNA文庫(kù)中比對(duì),獲得一條片段序列,用RACE方法獲得全長(zhǎng)序列,即。后續(xù)研究表明在分泌型腺毛中特異性表達(dá),對(duì)有正調(diào)控作用,過(guò)表達(dá)青蒿素及二氫青蒿酸含量分別上升40%~53%和22%~35%,同時(shí)能提高黃花蒿對(duì)灰霉病菌的抗性。

3.2.2 黃花蒿基因() 薄荷與萜類合成相關(guān)[50],Kayani等[51]以YABBY家族轉(zhuǎn)錄因子保守結(jié)構(gòu)域在黃花蒿基因組數(shù)據(jù)庫(kù)中查詢,將獲得的序列與構(gòu)建系統(tǒng)進(jìn)化樹(shù),同源性最高的序列即。后續(xù)研究表明能受MeJA的誘導(dǎo),直接結(jié)合、的啟動(dòng)子,提高青蒿素合成途徑基因當(dāng)?shù)霓D(zhuǎn)錄水平,過(guò)表達(dá)可以使青蒿素及二氫青蒿酸的含量升高。

4 轉(zhuǎn)錄組、基因組數(shù)據(jù)分析

4.1 黃花蒿TAR1基因(AaTAR1)

Graham等[52]對(duì)黃花蒿的遺傳圖譜進(jìn)行分析的文章中,預(yù)測(cè)了7個(gè)可能與腺毛發(fā)育相關(guān)的基因,Tan等[53]通過(guò)分析黃花蒿轉(zhuǎn)錄組數(shù)據(jù)及同源比對(duì),篩選出其中的1個(gè)AP2/ERF家族轉(zhuǎn)錄因子,命名為AaTAR1。后續(xù)研究表明AaTAR1可以控制蠟質(zhì)、角質(zhì)物質(zhì)的合成,能直接影響分泌型腺毛的形態(tài)發(fā)育,并通過(guò)結(jié)合青蒿素合成路徑上的基因啟動(dòng)子,來(lái)控制青蒿素的合成。過(guò)表達(dá)能提高青蒿素合成途徑基因的轉(zhuǎn)錄水平,并提高黃花蒿葉片和花蕾中青蒿素、青蒿酸及二氫青蒿酸的含量。

4.2 黃花蒿SPL2基因(AaSPL2)

在模式植物擬南芥中,有研究表明SPL轉(zhuǎn)錄因子參與調(diào)控植物的次生代謝[54-55]。Lv等[56]以SPL家族轉(zhuǎn)錄因子保守結(jié)構(gòu)域在黃花蒿轉(zhuǎn)錄組數(shù)據(jù)庫(kù)中查詢,得到14個(gè)結(jié)果,其中含有MicroRNA156識(shí)別位點(diǎn)的9條;用JA處理黃花蒿,檢測(cè)9條SPL轉(zhuǎn)錄因子基因的表達(dá)水平發(fā)現(xiàn)和響應(yīng)了JA信號(hào),其中的表達(dá)模式與青蒿素合成途徑基因的表達(dá)模式更為接近,因此選擇作為目的基因。后續(xù)研究表明,基因可激活的轉(zhuǎn)錄,從而介導(dǎo)JA對(duì)青蒿素合成的調(diào)控,過(guò)表達(dá)能提高青蒿素合成途徑基因的轉(zhuǎn)錄水平,使青蒿素和二氫青蒿酸的含量提高33%~86%和26%~159%。

4.3 黃花蒿GSW1基因(AaGSW1)

多條WRKY家族轉(zhuǎn)錄因子已被證實(shí)參與調(diào)控青蒿素的生物合成,但它們均非腺毛特異表達(dá)轉(zhuǎn)錄因子,Chen等[57]以WRKY保守結(jié)構(gòu)域序列在青蒿各組織轉(zhuǎn)錄組數(shù)據(jù)庫(kù)中比對(duì),共獲得122條序列,其中42條能在腺毛中表達(dá),通過(guò)與腺毛特異表達(dá)基因,如、等,在各組織中的表達(dá)模式進(jìn)行比較,獲得表達(dá)模式最為接近的1條,命名為。后續(xù)研究表明AaGSW1是腺毛特異表達(dá)轉(zhuǎn)錄因子,受JA信號(hào)途徑中的AaMYC2和ABA信號(hào)途徑的AabZip1調(diào)控,過(guò)表達(dá)能提高及的轉(zhuǎn)錄水平,使青蒿素含量提高39%~43%。

4.4 黃花蒿NAC1基因(AaNAC1)

NAC家族轉(zhuǎn)錄因子在提高植物對(duì)灰霉病菌抗性,及調(diào)控萜類物質(zhì)合成方面發(fā)揮作用[58-59]。Lv等[60]分析分泌性腺毛轉(zhuǎn)錄組數(shù)據(jù)庫(kù),選出RPKM(Reads Per Kilobase per Million mapped reads)值最高的10條NAC家族轉(zhuǎn)錄因子基因序列,其中能受SA和MeJA的誘導(dǎo),作為目的基因進(jìn)行研究。后續(xù)研究發(fā)現(xiàn)能受脫水、低溫、SA、MeJA的誘導(dǎo),過(guò)表達(dá)能使青蒿素和二氫青蒿酸的含量升高,提高黃花蒿對(duì)干旱、灰霉病菌的抗性。

5 展望

青蒿素是中醫(yī)藥對(duì)世界的重大貢獻(xiàn),隨著新適應(yīng)癥的開(kāi)發(fā),青蒿素的需求量會(huì)進(jìn)一步增大,解析青蒿素的合成路徑及調(diào)控網(wǎng)絡(luò),并利用分子育種的手段獲得高青蒿素含量的黃花蒿意義重大。青蒿素的產(chǎn)量與分泌性腺毛的發(fā)育情況密切相關(guān),同時(shí)黃花蒿也被認(rèn)為是研究分泌性腺毛發(fā)育的潛在模式植物,而轉(zhuǎn)錄因子無(wú)論在青蒿素的生物合成途徑中,還是在腺毛的發(fā)育過(guò)程中均具有關(guān)鍵的調(diào)控作用,因此轉(zhuǎn)錄因子是研究的重要靶標(biāo)。目前對(duì)黃花蒿轉(zhuǎn)錄因子的研究雖然已經(jīng)涉及到AP2/ERF、WRKY、MYB、bZip、bHLH等多個(gè)家族,但植物轉(zhuǎn)錄因子數(shù)量龐大,調(diào)控網(wǎng)絡(luò)復(fù)雜,當(dāng)前對(duì)黃花蒿轉(zhuǎn)錄因子調(diào)控作用的認(rèn)識(shí)仍相對(duì)有限。隨著研究技術(shù)手段的發(fā)展,特別是轉(zhuǎn)錄組、基因組等組學(xué)技術(shù)及單細(xì)胞測(cè)序等最新技術(shù)開(kāi)始應(yīng)用在黃花蒿的研究中,將更有利于發(fā)掘重要的功能基因,完善對(duì)青蒿素生物合成、分泌性腺毛發(fā)育等重要科學(xué)問(wèn)題的認(rèn)識(shí)。

利益沖突 所有作者均聲明不存在利益沖突

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Research on transcription factors related to artemisinin biosynthesis in

LI Qi, GAO Xiao-yue, ZHANG Lei, CHEN Wan-sheng, TAN He-xin

School of Pharmacy, Navy Medical University, Shanghai 200433, China

Artemisinin-based combination therapy is the preferred treatment for malaria. The medicinal plantis the only natural source and the main source of artemisinin. It is a hotspot to cultivate a strain ofwith high artemisinin content. Artemisinin is a secondary metabolite of. In the process of plant secondary metabolism, transcription factors play important roles in regulating a series of genes in the metabolic pathway, thereby regulating the direction and speed of metabolic flow. Therefore, the intervention of transcription factor by genetic engineering is an important method to regulate plant secondary metabolism. This article summarizes the functions and regulatory mechanism of transcription factors had been studied in. In particular, the methods for screening these transcription factors genes were summarized in order to provide a reference for the finding of key functional genes.

L.; artemisinin; transcription factor; metabolic regulation; secondary metabolite

R282.12

A

0253 - 2670(2021)06 - 1827 - 08

10.7501/j.issn.0253-2670.2021.06.032

2020-06-03

國(guó)家自然科學(xué)基金資助項(xiàng)目(81673529);科技部新藥創(chuàng)制重大專項(xiàng)(2017ZX09101002-003-002)

李 琦(1992—),男,碩士研究生,研究方向?yàn)橹兴幉钠焚|(zhì)改良。E-mail: liqi0121@163.com

譚何新,女,副教授,博士,碩士生導(dǎo)師,主要從事中藥資源研究。Tel/Fax: (021)81871370 E-mail: hexintan@163.com

[責(zé)任編輯 時(shí)圣明]

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