探讨中药功效成分合成生物学研究进展(4)
作者:佚名; 更新时间:2017-10-16

  尽管利用合成生物学生产中药功效成分近几年取得了很大进展,但这一领域同样存在很大的困难和问题,最主要的是目标产物的产量达不到工业化的需求,很多中药功效成分的合成还处于实验室合成阶段,在产量比较低的情况,造成目的产物生产成本比较高,因此目前而言,合成生物学技术生产功效成分适用于那些资源短缺、植物中含量低且比较贵重的中药功效成分。另外,中药功效成分生源合成途径的解析限制了利用合成生物学进行生产这些成分,尽管目前已有青蒿素、人参皂苷等成分的合成途径解析,但是中药大部分功效成分的解析依然存在很大的困难,进展缓慢,这严重限制了合成生物学在合成中药功效成分上的利用,因此实现目标产物产量的提高和更多中药功效成分生物合成途径的解析应是未来合成生物学生产中药功效成分的重点研究方向。

  [参考文献]

  [1] Julsing M K, Koulman A, Woerdenbag H J, et al. Combinatorial biosynthesis of medicinal plant secondary metabolites[J]. Biomol Eng, 2006, 23(6):265.

  [2] Qiu J. Traditional medicine:a culture in the balance[J]. Nature, 2007, 448(7150):126.

  [3] Sakurai Y, Kolokoltsov A A, Chen C C, et al. Twopore channels control Ebola virus host cell entry and are drug targets for disease treatment[J]. Science, 2015, 347(6225):995.

  [4] Liu J, Lee J, Hernandez M A S, et al. Treatment of obesity with celastrol[J]. Cell, 2015, 161(5):999.

  [5] Wang P, Wei Y, Fan Y, et al. Production of bioactive ginsenosides Rh2 and Rg3 by metabolically engineered yeasts[J]. Metab Eng, 2015, 29:97.

  [6] 陈士林,宋经元.本草基因组学[J].中国中药杂志,2016,41(21):3381.

  [7] Martin V J J, Pitera D J, Withers S T, et al. Engineering a mevalonate pathway in Escherichia coli for production of terpenoids[J]. Nat Biotechnol, 2003, 21(7):796.

  [8] Tsuruta H, Paddon C J, Eng D, et al. Highlevel production of amorpha4, 11diene, a precursor of the antimalarial agent artemisinin, in Escherichia coli[J]. PLoS ONE, 2009, 4(2):e4489.

  [9] Ro D K, Paradise E M, Ouellet M, et al. Production of the antimalarial drug precursor artemisinic acid in engineered yeast[J]. Nature, 2006, 440(7086):940.

  [10] Lindahl A L, Olsson M E, Mercke P, et al. Production of the artemisinin precursor amorpha4, 11diene by engineered Saccharomyces cerevisiae[J]. Biotechnol Lett, 2006, 28(8):571.

  [11] Zhang Y, Teoh K H, Reed D W, et al. The molecular cloning of artemisinic aldehyde Delta11(13) reductase and its role in glandular trichomedependent biosynthesis of artemisinin in Artemisia annua[J]. J Biol Chem, 2008, 283(31):21501.

  [12] Donald K A, Hampton R Y, Fritz I B. Effects of overproduction of the catalytic domain of 3hydroxy3methylglutaryl coenzyme A reductase on squalene synthesis in Saccharomyces cerevisiae[J]. Appl Environ Microbiol, 1997, 63(9):3341.

  [13] Pitera D J, Paddon C J, Newman J D, et al. Balancing a heterologous mevalonate pathway for improved isoprenoid production in Escherichia coli [J]. Metab Eng, 2007, 9(2):193.

  [14] Graham I A, Besser K, Blumer S, et al. The genetic map of Artemisia annua L. identifies loci affecting yield of the antimalarial drug artemisinin[J]. Science, 2010, 327(5963):328.

  [15] Singh N D, Kumar S, Daniell H. Expression of βglucosidase increases trichome density and artemisinin content in transgenic Artemisia annua plants[J]. Plant Biotechnol J, 2015, 14(3):1034.

  [16] Zhan Y, Liu H, Wu Y, et al. Biotransformation of artemisinin by Aspergillus niger[J]. Appl Microbiol Biotechnol, 2015, 99(8):3443.

  [17] Paddon C J, Westfall P J, Pitera D J, et al. Highlevel semisynthetic production of the potent antimalarial artemisinin[J]. Nature, 2013, 496(7446):528.

  [18] Phillipson J D. Phytochemistry and pharmacognosy[J]. Phytochemistry, 2007, 68(22):2960.

  [19] Wani M C, Taylor H L, Wall M E, et al. Plant antitumor agents. VI. Isolation and structure of taxol, a novel antileukemic and antitumor agent from Taxus brevifolia[J]. J Am Chem Soc, 1971, 93(9):2325.

  [20] Zaiyou J, Li M, Guifang X, et al. Isolation of an endophytic fungus producing baccatin Ⅲ from Taxus wallichiana var. mairei[J]. J Ind Microbiol Biotechnol, 2013, 40(11):1297.

  [21] Jennewein S, Croteau R. Taxol:biosynthesis, molecular genetics, and biotechnological applications[J]. Appl Microbiol Biotechnol, 2001, 57(1/2):13.

  [22] Altavilla A, Iacovelli R, Procopio G, et al. Medical strategies for treatment of castration resistant prostate cancer (CRPC) docetaxel resistant[J]. Cancer Biol Ther, 2012, 13(11):1001.

  [23] Denis J N, Greene A E, Guenard D, et al. Highly efficient, practical approach to natural taxol[J]. J Am Chem Soc, 1988, 110(17):5917.

  [24] Huang Q, Roessner C A, Croteau R, et al. Engineering Escherichia coli for the synthesis of taxadiene, a key intermediate in the biosynthesis of taxol[J]. Bioorg Med Chem, 2001, 9(9):2237.

  [25] Ajikumar P K, Xiao W H, Tyo K E J, et al. Isoprenoid pathway optimization for taxol precursor overproduction in Escherichia coli[J]. Science, 2010, 330(6000):70.

  [26] Zhou K, Qiao K, Edgar S, et al. Distributing a metabolic pathway among a microbial consortium enhances production of natural products[J]. Nat Biotechnol, 2015, 33(4):377.

  [27] 何道同,王兵,陈瑁明.人参皂苷药理作用研究进展[J].辽宁中医药大学学报,2012,14(7):118.

  [28] Dai Z, Yi L, Zhang X, et al. Metabolic engineering of Saccharomyces cerevisiae for production of ginsenosides[J]. Metab Eng, 2013, 20(5):146.

  [29] Dai Z, Wang B, Liu Y, et al. Producing aglycons of ginsenosides in bakers′ yeast[J]. Sci Rep, 2014, 4(4):3698.

  [30] Robertson A L, Holmes G R, Bojarczuk A N, et al. A zebrafish compound screen reveals modulation of neutrophil reverse migration as an antiinflammatory mechanism[J]. Sci Transl Med, 2014, 6(225):225ra29.

  [31] Dong Y, MorrisNatschke S L, Lee K H. Biosynthesis, total syntheses, and antitumor activity of tanshinones and their analogs as potential therapeutic agents[J]. Nat Prod Rep, 2011, 28(3):529.

  [32] Dai Z, Liu Y, Huang L, et al. Production of miltiradiene by metabolically engineered Saccharomyces cerevisiae[J]. Biotechnol Bioeng, 2012, 109(11):2845.

  [33] 高伟. 丹参酮类化合物生物合成相关酶基因克隆及功能研究 [D]. 北京:中国中医科学院, 2008.

  [34] Gao W, Hillwig M L, Huang L, et al. A functional genomics approach to tanshinone biosynthesis provides stereochemical insights[J]. Org Lett, 2009, 11(22):5170.

  [35] Guo J, Zhou Y J, Hillwig M L, et al. CYP76AH1 catalyzes turnover of miltiradiene in tanshinones biosynthesis and enables heterologous production of ferruginol in yeasts[J]. Proc Natl Acad Sci USA, 2013, 110(29):12108..

  [36] Guo J, Ma X, Cai Y, et al. Cytochrome P450 promiscuity leads to a bifurcating biosynthetic pathway for tanshinones[J]. New Phytologist, 2016, 210(2);525.

  [37] Qu Z, Zhou Y, Zeng Y, et al. Protective effects of a Rhodiola crenulata extract and salidroside on hippocampal neurogenesis against streptozotocininduced neural injury in the rat[J]. PLoS ONE, 2012, 7(1):e29641.

  [38] Yang Y, Liu Z, Feng Z, et al. Lignans from the root of Rhodiola crenulata[J]. J Agric Food Chem, 2012, 60(4):964.

  [39] Mao G X, Deng H B, Yuan L G, et al. Protective role of salidroside against aging in a mouse model induced by Dgalactose[J]. Biomed Environ Sci, 2010, 23(2):161.

  [40] Ouyang J F, Lou J, Yan C, et al. Invitro promoted differentiation of mesenchymal stem cells towards hepatocytes induced by salidroside[J]. J Pharm Pharmacol, 2010, 62(4):530.

  [41] Yan Z Y T. Ecological analysis on sexual reproductive produce and endangered reason of Rhodiola sachalinensis[J]. Bull Botan Res, 1998,18(3):336.

  [42] Satoh Y, Tajima K, Munekata M, et al. Engineering of a tyrosolproducing pathway, utilizing simple sugar and the central metabolic tyrosine, in Escherichia coli[J]. J Agric Food Chem, 2012, 60(4):979.

  [43] Bai Y, Bi H, Zhuang Y, et al. Production of salidroside in metabolically engineered Escherichia coli[J]. Sci Rep, 2014, 4:6640.

  [44] Kong J Q, Wang W, Cheng K D, et al. Research progresses in synthetic biology of artemisinin[J]. Acta Pharm Sinica, 2013, 48(2):193.

  [45] King Z A, Lloyd C J, Feist A M, et al. Nextgeneration genomescale models for metabolic engineering[J]. Curr Opin Biotechnol, 2015, 35:23.

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