生物技术通报 ›› 2021, Vol. 37 ›› Issue (8): 25-34.doi: 10.13560/j.cnki.biotech.bull.1985.2021-0949
收稿日期:
2021-07-25
出版日期:
2021-08-26
发布日期:
2021-09-10
作者简介:
周正,男,博士,助理研究员,研究方向:药用植物天然产物合成途径解析;E-mail: 基金资助:
ZHOU Zheng1(), LI Qing2, CHEN Wan-sheng2(), ZHANG Lei3()
Received:
2021-07-25
Published:
2021-08-26
Online:
2021-09-10
摘要:
来源于药用植物的天然产物是现代药物研发和创新的重要源泉。关于药用植物天然产物的传统研究,主要是围绕其提取纯化、化学结构、合成和生物功能展开。随着基因组学、生物信息学、分子生物学、分子遗传学、合成生物学等学科的飞速发展和各学科之间的交叉融合越来越广泛,药用植物的天然产物研究出现了新的机遇。本文针对药用植物天然产物生物合成及关键催化酶的研究策略进行系统综述,从药用植物天然产物生物合成途径的推测、天然产物生物合成关键催化酶的发现与预测、酶的表达特征研究、体内酶功能研究、酶催化特征研究、酶结构解析与优化、合成生物学研究这6个方面进行总结,并对未来药用植物天然产物合成途径及关键催化酶的发展趋势进行展望。
周正, 李卿, 陈万生, 张磊. 药用植物天然产物生物合成途径及关键催化酶的研究策略[J]. 生物技术通报, 2021, 37(8): 25-34.
ZHOU Zheng, LI Qing, CHEN Wan-sheng, ZHANG Lei. Research Strategies of Natural Products Biosynthesis Pathways and Key Enzymes in Medicinal Plants[J]. Biotechnology Bulletin, 2021, 37(8): 25-34.
[1] |
Eisenreich W, Menhard B, Hylands PJ, et al. Studies on the biosynjournal of taxol:the taxane carbon skeleton is not of mevalonoid origin[J]. PNAS, 1996, 93(13):6431-6436.
pmid: 8692832 |
[2] | Robins RJ, Woolley JG, Ansarin M, et al. Phenyllactic acid but not tropic acid is an intermediate in the biosynjournal of tropane alkaloids in Datura and Brugmansia transformed root cultures[J]. Planta, 1994, 194(1):86-94. |
[3] |
Di P, Zhang L, Chen J, et al. 13C tracer reveals phenolic acids biosynjournal in hairy root cultures of Salvia miltiorrhiza[J]. ACS Chem Biol, 2013, 8(7):1537-1548.
doi: 10.1021/cb3006962 URL |
[4] |
Guo J, Zhou YJ, Hillwig ML, et al. CYP76AH1 catalyzes turnover of miltiradiene in tanshinones biosynjournal and enables heterologous production of ferruginol in yeasts[J]. PNAS, 2013, 110(29):12108-12113.
doi: 10.1073/pnas.1218061110 URL |
[5] |
Vogt T. Phenylpropanoid biosynjournal[J]. Mol Plant, 2010, 3(1):2-20.
doi: 10.1093/mp/ssp106 URL |
[6] |
Bergman ME, Davis B, Phillips MA. Medically useful plant terpenoids:biosynjournal, occurrence, and mechanism of action[J]. Molecules, 2019, 24(21):3961.
doi: 10.3390/molecules24213961 URL |
[7] |
Winkel-Shirley B. Flavonoid biosynjournal. A colorful model for genetics, biochemistry, cell biology, and biotechnology[J]. Plant Physiol, 2001, 126(2):485-493.
pmid: 11402179 |
[8] |
Panjikar S, Stoeckigt J, O’Connor S, et al. The impact of structural biology on alkaloid biosynjournal research[J]. Nat Prod Rep, 2012, 29(10):1176-1200.
doi: 10.1039/c2np20057k pmid: 22907740 |
[9] |
Anttila M, Strangman W, York R, et al. Biosynthetic studies of 13-desmethylspirolide C produced by Alexandrium ostenfeldii(= A. peruvianum):rationalization of the biosynthetic pathway following incorporation of 13C-labeled methionine and application of the odd-even rule of methylation[J]. J Nat Prod, 2016, 79(3):484-489.
doi: 10.1021/acs.jnatprod.5b00869 URL |
[10] |
Gerardy R, Zenk MH. Purification and characterization of salutaridine:NADPH 7-oxidoreductase from Papaver somniferum[J]. Phytochemistry, 1993, 34(1):125-132.
doi: 10.1016/S0031-9422(00)90793-3 URL |
[11] |
Lenz R, Zenk MH. Acetyl coenzyme A:salutaridinol-7-O-acetyltransferase from Papaver somniferum plant cell cultures. The enzyme catalyzing the formation of thebaine in morphine biosynjournal[J]. J Biol Chem, 1995, 270(52):31091-31096.
pmid: 8537369 |
[12] |
Galanie S, Thodey K, Trenchard IJ, et al. Complete biosynjournal of opioids in yeast[J]. Science, 2015, 349(6252):1095-1100.
doi: 10.1126/science.aac9373 URL |
[13] |
Li Q, Chen J, Xiao Y, et al. The dirigent multigene family in Isatis indigotica:gene discovery and differential transcript abundance[J]. BMC Genomics, 2014, 15:388.
doi: 10.1186/1471-2164-15-388 URL |
[14] |
Xiao Y, Ji Q, Gao S, et al. Combined transcriptome and metabolite profiling reveals that IiPLR1 plays an important role in lariciresinol accumulation in Isatis indigotica[J]. J Exp Bot, 2015, 66(20):6259-6271.
doi: 10.1093/jxb/erv333 URL |
[15] | 肖莹. 菘蓝木脂素类成分生物合成关键调控因子的发现与功能评价[D]. 上海:上海中医药大学, 2015. |
Xiao Y. Discovery and functional evaluation of key regulatory factors for lignan biosynthesis of Isatis indigotica[D]. Shanghai:Shanghai University of Traditional Chinese Medicine, 2015. | |
[16] |
Wang S, Wang RS, Liu T, et al. CYP76B74 catalyzes the 3’-hydroxylation of geranylhydroquinone in shikonin biosynjournal[J]. Plant Physiol, 2019, 179(2):402-414.
doi: 10.1104/pp.18.01056 URL |
[17] |
Zhao Q, Yang J, Cui MY, et al. The reference genome sequence of Scutellaria baicalensis provides insights into the evolution of wogonin biosynjournal[J]. Mol Plant, 2019, 12(7):935-950.
doi: 10.1016/j.molp.2019.04.002 URL |
[18] |
Ma Y, Cui G, Chen T, et al. Expansion within the CYP71D subfamily drives the heterocyclization of tanshinones synjournal in Salvia miltiorrhiza[J]. Nat Commun, 2021, 12(1):685.
doi: 10.1038/s41467-021-20959-1 URL |
[19] |
Guo L, Winzer T, et al. The opium poppy genome and morphinan production[J]. Science, 2018, 362(6412):343-347.
doi: 10.1126/science.aat4096 pmid: 30166436 |
[20] |
Fu R, Zhang P, Jin G, et al. Versatility in acyltransferase activity completes chicoric acid biosynjournal in purple coneflower[J]. Nat Commun, 2021, 12(1):1563.
doi: 10.1038/s41467-021-21853-6 URL |
[21] |
Tu L, Su P, Zhang Z, et al. Genome of Tripterygium wilfordii and identification of cytochrome P450 involved in triptolide biosynjournal[J]. Nat Commun, 2020, 11(1):971.
doi: 10.1038/s41467-020-14776-1 URL |
[22] |
Qiu F, Zeng J, Wang J, et al. Functional genomics analysis reveals two novel genes required for littorine biosynjournal[J]. New Phytol, 2020, 225(5):1906-1914.
doi: 10.1111/nph.v225.5 URL |
[23] |
Ma W, Wu M, Wu Y, et al. Cloning and characterisation of a phenylalanine ammonia-lyase gene from Rhus chinensis[J]. Plant Cell Rep, 2013, 32(8):1179-1190.
doi: 10.1007/s00299-013-1413-6 URL |
[24] |
Su H, Liu Y, Xiao Y, et al. Molecular and biochemical characterization of squalene synthase from Siraitia grosvenorii[J]. Biotechnol Lett, 2017, 39(7):1009-1018.
doi: 10.1007/s10529-017-2328-z URL |
[25] |
Wang Z, Wang S, Xu Z, et al. Highly promiscuous flavonoid 3- O-glycosyltransferase from Scutellaria baicalensis[J]. Org Lett, 2019, 21(7):2241-2245.
doi: 10.1021/acs.orglett.9b00524 URL |
[26] |
Gao L, Su C, Du X, et al. FAD-dependent enzyme-catalysed intermolecular[4+2]cycloaddition in natural product biosynjournal[J]. Nat Chem, 2020, 12(7):620-628.
doi: 10.1038/s41557-020-0467-7 URL |
[27] |
Wu N, Jian D, Xiang M, et al. Biochemical characterization reveals the functional divergence of two tropinone reductases from Przewalskia tangutica[J]. Biotechnol Appl Biochem, 2019, 66(4):597-606.
doi: 10.1002/bab.v66.4 URL |
[28] |
Yu HS, Ma LQ, et al. Characterization of glycosyltransferases responsible for salidroside biosynjournal in Rhodiola sachalinensis[J]. Phytochemistry, 2011, 72(9):862-870.
doi: 10.1016/j.phytochem.2011.03.020 URL |
[29] |
Xiang BB, Li XX, Wang Y, et al. Cloning and characterization of two iridoid synthase homologs from Swertia mussotii[J]. Molecules, 2017, 22(8):1387.
doi: 10.3390/molecules22081387 URL |
[30] |
Zhou Z, Tan H, Li Q, et al. CRISPR/Cas9-mediated efficient targeted mutagenesis of RAS in Salvia miltiorrhiza[J]. Phytochemistry, 2018, 148:63-70.
doi: 10.1016/j.phytochem.2018.01.015 URL |
[31] |
Li B, Cui G, Shen G, et al. Targeted mutagenesis in the medicinal plant Salvia miltiorrhiza[J]. Sci Rep, 2017, 7:43320.
doi: 10.1038/srep43320 URL |
[32] |
Dinkins RD, Hancock J, Coe BL, et al. Isoflavone levels, nodulation and gene expression profiles of a CRISPR/Cas9 deletion mutant in the isoflavone synthase gene of red clover[J]. Plant Cell Rep, 2021, 40(3):517-528.
doi: 10.1007/s00299-020-02647-4 pmid: 33389047 |
[33] |
Zhao C, Xu TH, Liang YL, et al. Functional analysis of β-amyrin synthase gene in ginsenoside biosynjournal by RNA interference[J]. Plant Cell Rep, 2015, 34(8):1307-1315.
doi: 10.1007/s00299-015-1788-7 pmid: 25899218 |
[34] |
Lu C, Zhao SJ, Wei GN, et al. Functional regulation of ginsenoside biosynjournal by RNA interferences of a UDP-glycosyltransferase gene in Panax ginseng and Panax quinquefolius[J]. Plant Physiol Biochem, 2017, 111:67-76.
doi: 10.1016/j.plaphy.2016.11.017 URL |
[35] |
Kumar SR, Rai A, Bomzan DP, et al. A plastid-localized Bona fide geranylgeranyl diphosphate synthase plays a necessary role in monoterpene indole alkaloid biosynjournal in Catharanthus roseus[J]. Plant J, 2020, 103(1):248-265.
doi: 10.1111/tpj.v103.1 URL |
[36] |
Yuan Y, Liu WH, Zhang QZ, et al. Overexpression of artemisinic aldehyde Δ11(13)reductase gene-enhanced artemisinin and its relative metabolite biosynjournal in transgenicArtemisia annuaL[J]. Biotechnol Appl Biochem, 2015, 62(1):17-23.
doi: 10.1002/bab.1234 URL |
[37] |
Chung HH, Ting HM, Wang WH, et al. Elucidation of enzymes involved in the biosynthetic pathway of bioactive polyacetylenes in Bidens pilosa using integrated omics approaches[J]. J Exp Bot, 2021, 72(2):525-541.
doi: 10.1093/jxb/eraa457 URL |
[38] |
Wu YQ, Wang TL, Xin Y, et al. Overexpression of GbF3’5’H1 provides a potential to improve the content of epicatechin and gallocatechin[J]. Molecules, 2020, 25(20):4836.
doi: 10.3390/molecules25204836 URL |
[39] |
He JB, Zhao P, Hu ZM, et al. Molecular and structural characterization of a promiscuous C-glycosyltransferase from Trollius chinensis[J]. Angew Chem Int Ed Engl, 2019, 58(33):11513-11520.
doi: 10.1002/anie.v58.33 URL |
[40] |
Zhang M, Li FD, Li K, et al. Functional characterization and structural basis of an efficient di-C-glycosyltransferase from Glycyrrhiza glabra[J]. J Am Chem Soc, 2020, 142(7):3506-3512.
doi: 10.1021/jacs.9b12211 pmid: 31986016 |
[41] |
Xie K, Zhang X, et al. Exploring and applying the substrate promiscuity of a C-glycosyltransferase in the chemo-enzymatic synjournal of bioactive C-glycosides[J]. Nat Commun, 2020, 11(1):5162.
doi: 10.1038/s41467-020-18990-9 URL |
[42] |
Li J, Tian C, Xia Y, et al. Production of plant-specific flavones baicalein and scutellarein in an engineered E. coli from available phenylalanine and tyrosine[J]. Metab Eng, 2019, 52:124-133.
doi: 10.1016/j.ymben.2018.11.008 URL |
[43] |
Yao YF, Wang CS, Qiao J, et al. Metabolic engineering of Escherichia coli for production of salvianic acid A via an artificial biosynthetic pathway[J]. Metab Eng, 2013, 19:79-87.
doi: 10.1016/j.ymben.2013.06.001 URL |
[44] |
Srinivasan P, Smolke CD. Biosynjournal of medicinal tropane alkaloids in yeast[J]. Nature, 2020, 585(7826):614-619.
doi: 10.1038/s41586-020-2650-9 URL |
[45] |
Lau W, Sattely ES. Six enzymes from mayapple that complete the biosynthetic pathway to the etoposide aglycone[J]. Science, 2015, 349(6253):1224-1228.
doi: 10.1126/science.aac7202 URL |
[46] |
Schultz BJ, Kim SY, Lau W, et al. Total biosynjournal for milligram-scale production of etoposide intermediates in a plant chassis[J]. J Am Chem Soc, 2019, 141(49):19231-19235.
doi: 10.1021/jacs.9b10717 pmid: 31755709 |
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