香紫苏醇的微生物法生产研究进展
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摘要
香紫苏醇是一种植物次生代谢物,可从天然香紫苏醇等植物中提取,主要用于香紫苏内酯及降龙涎醚等天然龙涎香代用品的合成及香精的调配,还具有抗菌、杀菌活性等。由于生物技术的发展,利用微生物法合成香紫苏醇已引起国内外学者的广泛关注。本文概述了香紫苏醇及其衍生物的经济价值,并详细概述了微生物生产香紫苏醇的流程及研究状况。最后,本文还展望了微物生产法在香紫苏醇生产工业中应用前景及研究方向。尽管对微生物生产香紫苏醇的相关研究已取得了比较大的进步,但香紫苏醇合成的产率仍相对较低,因此,将分子生物学及代谢工程学手段融入到香紫苏醇合成及产业化应用的探索将是以后的研究重点。
Sclareol is a kind of secondary metabolite in plant,which can be extracted from Salvia sclare and utilized for production of sclareolide,ambroxide and perfume mixture. It can also be used as an efficient anti- microbe agent.The great advance in biology is making more and more scientists pay their attentions to biotechnological production of sclareol. The economic value of sclareol and its derivatives were briefly introduced,generalizing the procedures and present progresses of biotechnological production of sclareol. At last, the prospect of biotechnological methods in production of sclareol and research directions was also proposed. Although great progresses were obtained,the yield still remained relatively low,molecular biology and metabolic engineering in biotechnological production of sclareol and industrial application was considered to be the future focus in the long run.
Sclareol is a kind of secondary metabolite in plant,which can be extracted from Salvia sclare and utilized for production of sclareolide,ambroxide and perfume mixture. It can also be used as an efficient anti- microbe agent.The great advance in biology is making more and more scientists pay their attentions to biotechnological production of sclareol. The economic value of sclareol and its derivatives were briefly introduced,generalizing the procedures and present progresses of biotechnological production of sclareol. At last, the prospect of biotechnological methods in production of sclareol and research directions was also proposed. Although great progresses were obtained,the yield still remained relatively low,molecular biology and metabolic engineering in biotechnological production of sclareol and industrial application was considered to be the future focus in the long run.
引文
[1]FUJIMOTO T,MIZUKUBO T,ABE H.Sclareol induces plant resistance to root-knot nematote partially through ethylene-dependent enhancement of ligin accumulation[J].Molecular Plant-Microbe Interacions,2015(28):398-407.
[2]BHATIA SP,MCGINTY D,LETIZIA CS.Fragrance material review of sclareol[J].Food and Chemical Toxicology,2008(46):270-274.
[3]HATZIANTONIOU S,DIMAS K,GEORGOPOULOS A.Cytotoxic and antitumor activity of liposome-incorporated Sclareol against cancer cell lines and human colon cancer xenografts[J].Pharmacological Research,2006(53):80-87.
[4]DIMAS K,KOKKINOPOULOS D,DEMETZOS C.The effect of sclareol on growth and cell cycle progression of human leukemic cell lines[J].Leukemia Research,1999(23):217-234.
[5]DECORZANT R,VIAL C,WHITESIDES GM.A short synthesis of ambroxfrom sclareol[J].Tetrahedron,1987(43):1871-1879.
[6]ALEJANDRO FB,MANZANEDA EA,ALTAREJOS J.Synthesis of biologically active drimanes and homodrimanes from(-)-sclareol[J].Tetrahedron,1995(51):7435-7450.
[7]SCHALK M,PASTORE L,MIRATA MA.Toward a biosynthetic route to sclareol and amber odorants[J].Journal of the American Chemical Society,2012,134(46):18900-18903.
[8]ZERBE P,BOHLMANN J.Plant diterpene synthases:exploring modularity and metabolic diversity for bioengineering[J].Cell,2015(33):419-428.
[9]杨薇,周雍进,刘武军,等.构建酿酒酵母工程菌合成香紫苏醇[J].生物工程学报,2013,29(8):1185-1192.
[10]AJIKUMAR PK,XIAO WH,WANG Y.Isoprenoid pathway optimization for taxol precursor overproduction in Escherichia coli[J].Science,2010,330(6000):70-74.
[11]FARHI M,MARHEVKAA E,TANIAMASCIA.Harnessing yeast subcellular compartments for te production of plant terpenoids[J].Metabolic Engineering,2011(13):474-481.
[12]OHTO C,MURAMATSU M,OBATA S.Overexpression of the genecoding HGM-Co A reductase in saccaromyces cerevisiae for production of prenyl alcohol[J].Applied Microbiology Biotechnology,2009(82):837-845.
[13]IGNEA C,FOTINI A,ALEXANDROS K.Efficient diterpene production in yeast by engineering Erg20p into a geranylgeranyl diphosphate synthase[J].Metabolic Engineering,2015(27):65-75.
[14]GUO ZH,GEORGE J,WAGNER.Biosyntesis of labdanediol and sclareol in cell-free extracts from trichomes of Nicotiana glutinosa[J].Planta,1995(197):627-632.
[15]PADDON CJ,WESTFALL PJ,PITERA DJ.High-level semisynthetic production of the potent antimalarial artemisinin[J].Nature,2013(496):528-532.
[16]MARTIN VJJ,NEWMAN JD,KEASLING JD.Engineering a mevalonate pathway in Escherichia coli for production of Terpenoids[J].Nature Biotechnology,2003(21):796-802.
[17]ZENG Q,LIU F,YUAN L.Production of artemisinin by geneticallymodified microbes[J].Biotechnology Letters,2008(30):581-592.
[18]CURT RF,MARCUSCHAMER DK,STEPHANOPOULOS G.Selection and optimization of microbial hosts for biofuels production[J].Metabolic Engineering,2008(10):295-304.
[19]MUKHOPADHYAY,AINDRILA,KEASLING JD.Importance of systems biology in engineering microbes for biofuel production[J].Current Opinion in Biotechnology,2008(19):228-234.
[20]FRIJA LMT,RAQUEL FMF,CARLOS AMA.Isolation,chemical and biotransformation routes of labdane-type diterpenes[J].Chemical of Review,2011(111):4418-4452.
[2]BHATIA SP,MCGINTY D,LETIZIA CS.Fragrance material review of sclareol[J].Food and Chemical Toxicology,2008(46):270-274.
[3]HATZIANTONIOU S,DIMAS K,GEORGOPOULOS A.Cytotoxic and antitumor activity of liposome-incorporated Sclareol against cancer cell lines and human colon cancer xenografts[J].Pharmacological Research,2006(53):80-87.
[4]DIMAS K,KOKKINOPOULOS D,DEMETZOS C.The effect of sclareol on growth and cell cycle progression of human leukemic cell lines[J].Leukemia Research,1999(23):217-234.
[5]DECORZANT R,VIAL C,WHITESIDES GM.A short synthesis of ambroxfrom sclareol[J].Tetrahedron,1987(43):1871-1879.
[6]ALEJANDRO FB,MANZANEDA EA,ALTAREJOS J.Synthesis of biologically active drimanes and homodrimanes from(-)-sclareol[J].Tetrahedron,1995(51):7435-7450.
[7]SCHALK M,PASTORE L,MIRATA MA.Toward a biosynthetic route to sclareol and amber odorants[J].Journal of the American Chemical Society,2012,134(46):18900-18903.
[8]ZERBE P,BOHLMANN J.Plant diterpene synthases:exploring modularity and metabolic diversity for bioengineering[J].Cell,2015(33):419-428.
[9]杨薇,周雍进,刘武军,等.构建酿酒酵母工程菌合成香紫苏醇[J].生物工程学报,2013,29(8):1185-1192.
[10]AJIKUMAR PK,XIAO WH,WANG Y.Isoprenoid pathway optimization for taxol precursor overproduction in Escherichia coli[J].Science,2010,330(6000):70-74.
[11]FARHI M,MARHEVKAA E,TANIAMASCIA.Harnessing yeast subcellular compartments for te production of plant terpenoids[J].Metabolic Engineering,2011(13):474-481.
[12]OHTO C,MURAMATSU M,OBATA S.Overexpression of the genecoding HGM-Co A reductase in saccaromyces cerevisiae for production of prenyl alcohol[J].Applied Microbiology Biotechnology,2009(82):837-845.
[13]IGNEA C,FOTINI A,ALEXANDROS K.Efficient diterpene production in yeast by engineering Erg20p into a geranylgeranyl diphosphate synthase[J].Metabolic Engineering,2015(27):65-75.
[14]GUO ZH,GEORGE J,WAGNER.Biosyntesis of labdanediol and sclareol in cell-free extracts from trichomes of Nicotiana glutinosa[J].Planta,1995(197):627-632.
[15]PADDON CJ,WESTFALL PJ,PITERA DJ.High-level semisynthetic production of the potent antimalarial artemisinin[J].Nature,2013(496):528-532.
[16]MARTIN VJJ,NEWMAN JD,KEASLING JD.Engineering a mevalonate pathway in Escherichia coli for production of Terpenoids[J].Nature Biotechnology,2003(21):796-802.
[17]ZENG Q,LIU F,YUAN L.Production of artemisinin by geneticallymodified microbes[J].Biotechnology Letters,2008(30):581-592.
[18]CURT RF,MARCUSCHAMER DK,STEPHANOPOULOS G.Selection and optimization of microbial hosts for biofuels production[J].Metabolic Engineering,2008(10):295-304.
[19]MUKHOPADHYAY,AINDRILA,KEASLING JD.Importance of systems biology in engineering microbes for biofuel production[J].Current Opinion in Biotechnology,2008(19):228-234.
[20]FRIJA LMT,RAQUEL FMF,CARLOS AMA.Isolation,chemical and biotransformation routes of labdane-type diterpenes[J].Chemical of Review,2011(111):4418-4452.