植物来源的二萜化合物的生物合成研究
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摘要
二萜化合物广泛地存在于动物、植物和微生物中。由于其化学结构多样性和良好的生物活性,越来越多的二萜类化合物作为药物走进大众的视野,并受到越来越多的科学工作者的关注。绝大多数的二萜化合物来源于植物,但是随着植物药材的长期开发,野生植物药材资源日益减少,人工种植植物药材品质日渐退化,而揭示其中关键活性成分的生物合成机制,以合成生物学的策略改造的微生物作为"细胞工厂",是解决上述问题的重要手段。该文主要以二萜合酶为线索,概述了植物来源的二萜类化合物的生物合成研究进展,探究二萜化合物结构的多样性及其生物合成研究的前景和发展趋势。
Diterpenoids widely exist in animals, plants and microorganisms. Due to their chemical structure diversity and remarkable biological activities, increasing amounts of diterpenoids have affected our lives as clinical drugs, and also have attracted more attentions from scientists. Most of the known diterpenoids are isolated from plants. However, with the long-term development of plant medicinal herbs, the resources of wild medicinal herbs are decreasing quickly, and the quality of herbs artificially planted is increasingly becoming degraded. The characterization of the biosynthetic pathways of key active ingredients of plants is a crucial step to solve the above problems in microorganisms as "cell factories" using synthetic biology strategies. With diterpene synthase as a clue,we summarized current progress in the biosynthesis of diterpenoids from plants, and explored the structure diversity of diterpenoids and the prospective and trends of the research on their biosynthesis.
Diterpenoids widely exist in animals, plants and microorganisms. Due to their chemical structure diversity and remarkable biological activities, increasing amounts of diterpenoids have affected our lives as clinical drugs, and also have attracted more attentions from scientists. Most of the known diterpenoids are isolated from plants. However, with the long-term development of plant medicinal herbs, the resources of wild medicinal herbs are decreasing quickly, and the quality of herbs artificially planted is increasingly becoming degraded. The characterization of the biosynthetic pathways of key active ingredients of plants is a crucial step to solve the above problems in microorganisms as "cell factories" using synthetic biology strategies. With diterpene synthase as a clue,we summarized current progress in the biosynthesis of diterpenoids from plants, and explored the structure diversity of diterpenoids and the prospective and trends of the research on their biosynthesis.
引文
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[5]Smanski MJ,Yu Z,Casper J,et al.Dedicated ent-kaurene and ent-atiserene synthases for platensimycin and platencin biosynthesis.Proc Natl Acad Sci USA,2011,108:13498-503
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[10]Miziorko HM.Enzymes of the mevalonate pathway of isoprenoid biosynthesis.Arch Biochem Biophys,2011,505:131-43
[11]Hunter WN.The non-mevalonate pathway of isoprenoid precursor biosynthesis.Biochem Soc Trans,2003,282:537-42
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[13]Banerjee A,Hamberger B.P450s controlling metabolic bifurcations in plant terpene specialized metabolism.Phytochem Rev,2018,17:81-111
[14]Falara V,Akhtar TA,Nguyen TT,et al.The tomato terpene synthase gene family.Plant Physiol,2011,157:770-89
[15]Christianson DW.Roots of biosynthetic diversity.Science,2007,316:60-1
[16]Tholl D.Terpene synthases and the regulation,diversity and biological roles of terpene metabolism.Curr Opin Plant Biol,2006,9:297-304
[17]Tholl D.Biosynthesis and biological functions of terpenoids in plants.Adv Biochem Eng Biotechnol,2015,148:63-106
[18]Xu M,Jia M,Hong YJ,et al.Premutilin synthase:ring rearrangement by a class II diterpene cyclase.Org Lett,2018,20:1200-2
[19]Toyomasu T,Tsukahara M,Kaneko A,et al.Fusicoccins are biosynthesized by an unusual chimera diterpene synthase in fungi.Proc Natl Acad Sci USA,2007,104:3084-8
[20]Minami A,Ozaki T,Liu C,et al.Cyclopentane-forming di/sesterterpene synthases:widely distributed enzymes in bacteria,fungi,and plants.Nat Prod Rep,2018,35:1330-46
[21]Yang YL,Zhang S,Ma K,et al.Discovery and characterization of a new family of diterpene cyclases in bacteria and fungi.Angew Chem Int Ed Engl,2017,129:4749-52
[22]Zerbe P,Bohlmann J.Plant diterpene synthases:exploring modularity and metabolic diversity for bioengineering.Trends in Biotechnol,2015,33:419-28
[23]Chen F,Tholl D,Bohlmann J,et al.The family of terpene synthases in plants:a mid-size family of genes for specialized metabolism that is highly diversified throughout the kingdom.Plant J,2011,66:212-29
[24]K?ksal M,Jin Y,Coates RM,et al.Taxadiene synthase structure and evolution of modular architecture in terpene biosynthesis.Nature,2011,469:116-20
[25]Mitsuhashi T,Okada M,Abe I.Identification of chimericαβγditerpene synthases possessing both type II terpene cyclase and prenyitransferase activities.Chembiochem,2017,18:2104-9
[26]Howat S,Park B,Oh IS,et al.Paclitaxel:biosynthesis,production and future prospects.Nat Biotechnol,2014,31:242-5
[27]Muchiri R,Walker KD.Taxol biosynthesis:tyrocidine synthetase A catalyzes the production of phenylisoserinyl CoA and other amino phenylpropanoyl thioesters.Chem Biol,2012,19:679-85
[28]Edgar S,Li FS,Qiao K,et al.Engineering of taxadiene synthase for improved selectivity and yield of a key taxol biosynthetic intermediate.ACS Synth Biol,2017,6:201-5
[29]Biggs BW,Lim CG,Sagliani K,et al.Overcoming heterologous protein interdependency to optimize P450-mediated Taxol precursor synthesis in Escherichia coli.Proc Natl Acad Sci USA,2016,113:3209-14
[30]Vaughan MM,Wang Q,Webster FX,et al.Formation of the unusual semivolatile diterpene rhizathalene by the Arabidopsis class I terpene synthase TPS08 in the root stele is involved in defense against belowground herbivory.Plant Cell,2013,25:1108-25
[31]Lauterbach L,Rinkel J,Dickschat JS.Two bacterial diterpene synthases from allokutzneria albata for bonnadiene and for phomopsene and allokutznerene.Angew Chem Int Ed Engl,2018,57:8280-3
[32]Rinkel J,Rabe P,Chen X,et al.Mechanisms of the diterpene cyclasesβ-pinacene synthase from dictyostelium discoideum and hydropyrene synthase from Streptomyces clavuligerus.Chemistry,2017,23:10501-5
[33]Mau CJ,West CA.Cloning of casbene synthase cDNA:evidence for conserved structural features among terpenoid cyclases in plants.Proc Natl Acad Sci USA,1994,91:8497-501
[34]Kirby J,Nishimoto M,Park JG,et al.Cloning of casbene and neocembrene synthases from Euphorbiaceae plants and expression in Saccharomyces cerevisiae.Phytochemistry,2010,71:1466-73
[35]King AJ,Graham IA.Production of bioactive diterpenoids in the euphorbiaceae depends on evolutionarily conserved gene clusters.Plant Cell,2014,26:3286-98
[36]Luo D,Callari R,Hamberger B,et al.Oxidation and cyclization of casbene in the biosynthesis of Euphorbia factors from mature seeds of Euphorbia lathyris L.Proc Natl Acad Sci USA,2016,113:E5082-9
[37]Gutensohn M,Nguyen TT,McMahon RD 3rd,et al.Metabolic engineering of monoterpene biosynthesis in tomato fruits via introduction of the non-canonical substrate neryl diphosphate.Metab Eng,2014,24:107-16
[38]Zi J,Matsuba Y,Hong YJ,et al.Biosynthesis of lycosantalonol,a cis-prenyl derived diterpenoid.J Am Chem Soc,2014,136:16951-3
[39]Matsuba Y,Zi J,Jones AD,et al.Biosynthesis of the diterpenoid lycosantalonol via nerylneryl diphosphate in Solanum lycopersicum.PLoS One,2015,10:e0119302
[40]Jia M,Potter KC,Peters RJ.Extreme promiscuity of a bacterial and a plant diterpene synthase enables combinatorial biosynthesis.Metab Eng,2016,37:24-34
[41]Silva L,Gomes AC,Rodilla JM.Diterpene lactones with labdane,halimane and clerodane frameworks.Nat Prod Commun,2011,6:497-504
[42]Cyr A,Wilderman PR,Determan M,et al.A modular approach for facile biosynthesis of labdane-related diterpenes.J Am Chem Soc,2007,129:6684-5
[43]Kitaoka N,Lu X,Yang B,et al.The application of synthetic biology to elucidation of plant mono-,sesqui-,and diterpenoid metabolism.Mol Plant,2015,8:6-16
[44]Arns S,Barriault L.Cascading pericyclic reactions:building complex carbon frameworks for natural product synthesis.Chem Commun,2007,2211-21
[45]Otomo K,Kanno Y,Motegi A,et al.Diterpene cyclases responsible for the biosynthesis of phytoalexins,momilactones A,B,and oryzalexins A-F in rice.Biosci Biotechnol Biochem,2004,68:2001-6
[46]Schmelz EA,Huffaker A,Sims JW,et al.Biosynthesis,elicitation and roles of monocot terpenoid phytoalexins.Plant J,2015,79:659-78
[47]Toyomasu T,Miyamoto K,Shenton MR,et al.Characterization and evolutionary analysis of ent-kaurene synthase like genes from the wild rice species Oryza rufipogon.Biochem Biophys Res Commun,2016,480:402-8
[48]Wilderman PR,Xu M,Jin Y,et al.Identification of syn-pimara-7,15-diene synthase reveals functional clustering of terpene synthases involved in rice phytoalexin/allelochemical biosynthesis.Plant Physiol,2004,135:2098-105
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