以小米为基质牛樟芝固态发酵高产antroquinonol的条件优化
|
摘要
为提高牛樟芝固态发酵产antroquinonol的能力,以不同谷物作为牛樟芝固态发酵基质,并对其高产antroquinonol的原因进行了初步分析。随后对发酵时间、初始含水量、接种量、外加氮源等进行单因素实验,并在此基础上用Design-Expert方法进行响应面分析。结果表明:固态基质为小米,接种量为21%,培养25 d,大豆水解液添加量为82. 4 mL/L,初始含水量为41%,antroquinonol产量为1 340. 7 mg/kg,是未优化前产量(325. 0mg/kg)的4. 1倍。该研究为牛樟芝固态发酵产活性物质的工业化应用提供了理论基础。
Antrodia cinnamomea is a medicinal and edible fungi that has significant biological activities. Antroquinonol is one of the characteristic products during solid-state fermentation of A. cinnamomea,and it has excellent anti-cancer effect. In order to improve the ability of A. cinnamomea to produce antroquinonol during fermentation,various kinds of grains were used as substrates,and millet was found to be the best. The fermentation time,initial moisture content,inoculation amount,and exogenous nitrogen source were systematically studied by single factor experiments,followed by process optimization by Design-Expert response surface design. The results showed that the best antroquinonol-producing condition was as follows: millet as the solid substrate,21% inoculation amount,82. 4 mL/L soybean hydrolysate,41% initial moisture content,and cultured for 25 d. Under this condition,the yield of antroquinonol was the highest to date( 1340. 7 mg/kg),which was 4. 1 times higher than that of control( 325. 0 mg/kg).This study provides a theoretical basis for industries to use A. cinnamomea that produces bioactive compounds by solid-state fermentation.
Antrodia cinnamomea is a medicinal and edible fungi that has significant biological activities. Antroquinonol is one of the characteristic products during solid-state fermentation of A. cinnamomea,and it has excellent anti-cancer effect. In order to improve the ability of A. cinnamomea to produce antroquinonol during fermentation,various kinds of grains were used as substrates,and millet was found to be the best. The fermentation time,initial moisture content,inoculation amount,and exogenous nitrogen source were systematically studied by single factor experiments,followed by process optimization by Design-Expert response surface design. The results showed that the best antroquinonol-producing condition was as follows: millet as the solid substrate,21% inoculation amount,82. 4 mL/L soybean hydrolysate,41% initial moisture content,and cultured for 25 d. Under this condition,the yield of antroquinonol was the highest to date( 1340. 7 mg/kg),which was 4. 1 times higher than that of control( 325. 0 mg/kg).This study provides a theoretical basis for industries to use A. cinnamomea that produces bioactive compounds by solid-state fermentation.
引文
[1] WUS H,RYVARDEN L,CHANG T T. Antrodia camphorata(niu-chang-chih),new combination of a medicinal fungus in Taiwan[J]. Botanical Bulletin-Academia Sinica Taipei,1996,38(4):273-275.
[2]张东柱.台湾特有珍贵药用真菌牛樟芝[J].食药用菌,2011,19(1):33-34.
[3] AO Z H,XU Z H,LU Z M,et al. Niuchangchih(Antrodia camphorata)and its potential in treating liver diseases[J].Journal of Ethnopharmacol,2009,121(2):194-212.
[4] GEETHANGILI M,TZENG Y M. Review of pharmacological effects of Antrodia camphorata and its bioactive compounds[J]. Evidence-Based Complementray and Alternative Medicine,2011,8(1):1-17.
[5]张薄博,夏永军,许赣荣.樟芝发酵产品的研究进展[J].食品科技,2012,37(10):89-91.
[6] LU M C,El S M,WU T Y,et al. Recent research and development of Antrodia cinnamomea[J]. Pharmacol Therapeut,2013,139(2):124-156.
[7]邢宏博,胡永丹,吕俊,等.樟芝活性代谢产物的研究进展[J].生物加工过程,2017,15(4):1-8.
[8] LEE T H,LEE C K,TSOU W L,et al. A new cytotoxic agent from solid-state fermented mycelium of Antrodia camphorata[J]. Planta Medica,2007,73(13):1 412.
[9] YANG S S,WANG G J,WANG S Y,et al. New constituents with i NOS inhibitory activity from mycelium of Antrodia camphorata[J]. Planta Medica,2009,75(5):512-516.
[10] LINY W,PAN J H,LIU R H,et al. The 4-acetylantroquinonol B isolated from mycelium of Antrodia cinnamomea inhibits proliferation of hepatoma cells[J]. Journal of the Science of Food and Agriculture,2010,90(10):1 739-1 744.
[11] YEN I C,YAO C W,KUO M T,et al. Anti-cancer agents derived from solid-state fermented Antrodia camphorata mycelium[J]. Fitoterapia,2015,102:115-119.
[12] YEN I,LEE S Y,LIN K T,et al. In vitro anticancer activity and structural characterization of ubiquinones from Antrodia cinnamomea mycelium[J]. Molecules,2017,22(5):747.
[13] KUMAR K J,CHU F H,HSIEN H W,et al. Antroquinonol from ethanolic extract of mycelium of Antrodia cinnamomea protects hepatic cells from ethanol-induced oxidative stress through Nrf-2 activation[J]. Journal of Ethnopharmacol,2011,136(1):168-177.
[14] KUMAR V B,YUAN T C,LIOU J W,et al. Antroquinonol inhibits NSCLC proliferation by altering PI3K/m TOR proteins and miRNA expression profiles[J]. Mutation Research,2011,707(1-2):42-52.
[15] YU C C,CHIANG P C,LU P H,et al. Antroquinonol,a natural ubiquinone derivative,induces a cross talk between apoptosis, autophagy and senescence in human pancreatic carcinoma cells[J]. Journal of Nutritional Biochemistry,2012,23(8):900-907.
[16] HO C L,WANG J L,LEE C C,et al. Antroquinonol blocks Ras and Rho signaling via the inhibition of protein isoprenyltransferase activity in cancer cells[J]. Biomedicine and Pharmacother,2014,68(8):1 007-1 014.
[17] CHANG W H,CHEN M C,CHENG I H. Antroquinonol lowers brain amyloid-βlevels and improves spatial learning and memory in a transgenic mouse model of Alzheimer’s disease[J]. Scientific Reports,2015,5:15 067.
[18] LEE W T,LEE T H,CHENG C H,et al. Antroquinonol from Antrodia camphorata suppresses breast tumor migration/invasion through inhibiting ERK-AP-1 and AKT-NFkappa B-dependent MMP-9 and epithelial-mesenchymal transition expressions[J]. Food Chemical Toxicol,2015,78:33-41.
[19] THIYAGARAJAN V,TSAI M J,WENG C F. Antroquinonol targets FAK-signaling pathway suppressed cell migration,invasion,and iumor growth of C6 glioma[J]. PLo S One,2015,10(10):e0141285.
[20] ANGAMUTHU V,SHANMUGAVADIVU M,NAGARAJAN G,et al. Pharmalogical activities of antroquinonolmini review[J]. Chemico-Biological Interactions,2019,297:8-15.
[21] VILLAUME M T,SELLA E,SAUL G,et al. Antroquinonol A:scalable synthesis and preclinical biology of a phase 2drug candidate[J]. ACS Central Science,2016,2(1):27-31.
[22]夏永军,张贤芳,许赣荣.牛樟芝培养技术的研究进展[J].食品科学,2012,33(11):185-189.
[23] DORIYA K,JOSE N,GOWDA M,et al. Solid-state fermentation vs submerged fermentation for the production of L-asparaginase[J]. Advances in Food and Nutrition Research,2016,78:115-135.
[24]喻学淳,夏永军,张欢,等.樟芝固态发酵生产Antroquinonol及萃取Antroquinonl的研究[J].食品工业科技,2013,34(5):164-168.
[25]路瑞秋,胡永丹,张薄博,等.响应面法优化樟芝固态发酵产安卓奎诺尔[J].食品科学,2015,36(23):150-154.
[26] XIA Y J,WANG Y,HANG B B,et al. Effect of cultural conditions on antrodin C production by basidiomycete Antrodia camphorata in solid-state fermentation[J]. Biotechnology and Applied Biochemistry,2015,61(6):724-732.
[27] ABDULLAH B,MAFTUKHAH S,LISTYANINGRUM E,et al. In Effect of some variable in cellulase production by Aspergillus niger ITBCC L74 using solid state fermentation[C],Materials Science and Engineering Conference Series,2018.
[28] HANAI H,ISHIDA S,SAITO C,et al. Stimulation of mycelia growth in several mushroom species by rice husks[J]. Bioscience Biotechnology and Biochemistry,2005,69(1):123-127.
[29] SRIANTA I,ZUBAIDAH E,ESTIASIH T,et al. Comparison of Monascus purpureus growth,pigment production and composition on different cereal substrates with solid state fermentation[J]. Biocatalysis and Agricultural Biotechnology,2016,7:181-186.
[30] TAKESHITA R,SAIGUSA N,TREAMOTO Y. Production and antioxidant activity of alcoholic beverages made from various cereal grains using Monascus purpureus NBRC5965[J]. Journal of the Institute of Brewing,2016,122(2):350-354.
[31] YANGF C,YANGY H,LU H C. Enhanced antioxidant and antitumor activities of Antrodia cinnamomea cultured with cereal substrates in solid state fermentation[J]. Biochemical Engineering Journal,2013,78(37):108-113.
[32] TEREBIZNIK M R,PILOSOF A M R. Biomass estimation in solid state fermentation by modeling dry matter weight loss[J]. Biotechnology Techniques,1999,13(3):215-219.
[33] MAZAHERI D,SHOJAOSADATI S A,ZAMIR S M,et al.Mathematical modeling of ethanol production in solid-state fermentation based on solid medium dry weight variation[J]. Preparative Biochemistry and Biotechnology,2018,48(4):372-377.
[34]丁雪,马晓燕,张先舟,等.降解游离棉酚的热带假丝酵母菌的发酵动力学研究[J].中国酿造,2011,30(6):131-134.
[35]夏永军,李炜疆,许赣荣.樟芝固态发酵产品活性代谢产物分析[J].食品与发酵工业,2011,37(8):86-90.
[36]段传玲,兰静,张宏坤.分光光度法测定大米直链淀粉含量的误差分析[J].黑龙江农业科学,2015(4):129-133.
[37] WEUSTER B D. Experimental design for fermentation media development:statistical design or global random search[J]. Journal of Bioscience and Bioengineering,2000,90(5):473-483.
[38] RASHID S S,ALAM M Z,KARIM M I A,et al. Optimization of the nutrient supplients for cellulase production with the basal medium palm oil mill effluent[J]. World Academy of Science, Engineering and Technology,2009,60(6):809-815.
[39]吕腾飞,丁彦蕊,廖祥儒,等.竹黄菌固态发酵产竹红菌素条件的优化[J].食品与生物技术学报,2013,32(8):832-837.
[40]蔡一霞,朱智伟,王维,等.直链淀粉含量与稻米品质主要性状及米饭质地关系的研究[J].扬州大学学报(农业与生命科学版),2005,26(4):52-55.
[41]刘爱英,孙伟,梁宗琦,等.不同米质发酵生产红曲对莫纳可林K含量的影响[J].贵州农业科学,2003,31(5):5-7.
[42]冯杉,江林芡,李赛楠,等.无机盐和维生素对固体培养槐耳菌丝生长影响的研究[J].中南药学,2015,13(6):591-593.
[43]张帅,陈懿,董基,等.黑曲霉固态发酵橘皮生产纤维素酶及淀粉酶[J].食品科学,2012,33(11):190-193.
[44] LOTONG N,SUWANARIT P. Fermentation of ang-kak in plastic bags and regulation of pigmentation by initial moisture content[J]. Journal of Applied Microbiology,2010,68(6):565-570.
[45] LARROCHE C,THEODORE M,GROS J B. Growth and sporulation behaviour of Penicillium roquefortii in solid substrate fermentation:effect of the hydric parameters of the medium[J]. Applied Microbiology and Biotechnology,1992,38(2):183-187.
[46]童爱均,吕旭聪,刘晓艳,等.固体发酵基质和外加碳氮源对红曲霉色素产量的影响[J].中国调味品,2015(5):5-10.
[47]杨晓婉,张娜,李雪霞,等.大豆蛋白及其水解物在乳粉中的应用及研究进展[J].中国乳品工业,2018,46(4):31-34.
[48]陶红,梁歧,张鸣镝.热处理对大豆蛋白水解液分子量的影响[J].食品科学,2003,24(11):18-22.
[49] TANYILDIZI M S,ELIBBOL O M. Optimization ofα-amylase production by Bacillus sp. using response surface methodology[J]. Process Biochemical,2005,40(7):2 291-2 296.
[50]鞠兴荣,王雪峰,王立峰,等.混菌固态发酵菜籽粕制备菜籽肽的菌种筛选[J].食品与发酵工业,2011,37(9):104-108.
[2]张东柱.台湾特有珍贵药用真菌牛樟芝[J].食药用菌,2011,19(1):33-34.
[3] AO Z H,XU Z H,LU Z M,et al. Niuchangchih(Antrodia camphorata)and its potential in treating liver diseases[J].Journal of Ethnopharmacol,2009,121(2):194-212.
[4] GEETHANGILI M,TZENG Y M. Review of pharmacological effects of Antrodia camphorata and its bioactive compounds[J]. Evidence-Based Complementray and Alternative Medicine,2011,8(1):1-17.
[5]张薄博,夏永军,许赣荣.樟芝发酵产品的研究进展[J].食品科技,2012,37(10):89-91.
[6] LU M C,El S M,WU T Y,et al. Recent research and development of Antrodia cinnamomea[J]. Pharmacol Therapeut,2013,139(2):124-156.
[7]邢宏博,胡永丹,吕俊,等.樟芝活性代谢产物的研究进展[J].生物加工过程,2017,15(4):1-8.
[8] LEE T H,LEE C K,TSOU W L,et al. A new cytotoxic agent from solid-state fermented mycelium of Antrodia camphorata[J]. Planta Medica,2007,73(13):1 412.
[9] YANG S S,WANG G J,WANG S Y,et al. New constituents with i NOS inhibitory activity from mycelium of Antrodia camphorata[J]. Planta Medica,2009,75(5):512-516.
[10] LINY W,PAN J H,LIU R H,et al. The 4-acetylantroquinonol B isolated from mycelium of Antrodia cinnamomea inhibits proliferation of hepatoma cells[J]. Journal of the Science of Food and Agriculture,2010,90(10):1 739-1 744.
[11] YEN I C,YAO C W,KUO M T,et al. Anti-cancer agents derived from solid-state fermented Antrodia camphorata mycelium[J]. Fitoterapia,2015,102:115-119.
[12] YEN I,LEE S Y,LIN K T,et al. In vitro anticancer activity and structural characterization of ubiquinones from Antrodia cinnamomea mycelium[J]. Molecules,2017,22(5):747.
[13] KUMAR K J,CHU F H,HSIEN H W,et al. Antroquinonol from ethanolic extract of mycelium of Antrodia cinnamomea protects hepatic cells from ethanol-induced oxidative stress through Nrf-2 activation[J]. Journal of Ethnopharmacol,2011,136(1):168-177.
[14] KUMAR V B,YUAN T C,LIOU J W,et al. Antroquinonol inhibits NSCLC proliferation by altering PI3K/m TOR proteins and miRNA expression profiles[J]. Mutation Research,2011,707(1-2):42-52.
[15] YU C C,CHIANG P C,LU P H,et al. Antroquinonol,a natural ubiquinone derivative,induces a cross talk between apoptosis, autophagy and senescence in human pancreatic carcinoma cells[J]. Journal of Nutritional Biochemistry,2012,23(8):900-907.
[16] HO C L,WANG J L,LEE C C,et al. Antroquinonol blocks Ras and Rho signaling via the inhibition of protein isoprenyltransferase activity in cancer cells[J]. Biomedicine and Pharmacother,2014,68(8):1 007-1 014.
[17] CHANG W H,CHEN M C,CHENG I H. Antroquinonol lowers brain amyloid-βlevels and improves spatial learning and memory in a transgenic mouse model of Alzheimer’s disease[J]. Scientific Reports,2015,5:15 067.
[18] LEE W T,LEE T H,CHENG C H,et al. Antroquinonol from Antrodia camphorata suppresses breast tumor migration/invasion through inhibiting ERK-AP-1 and AKT-NFkappa B-dependent MMP-9 and epithelial-mesenchymal transition expressions[J]. Food Chemical Toxicol,2015,78:33-41.
[19] THIYAGARAJAN V,TSAI M J,WENG C F. Antroquinonol targets FAK-signaling pathway suppressed cell migration,invasion,and iumor growth of C6 glioma[J]. PLo S One,2015,10(10):e0141285.
[20] ANGAMUTHU V,SHANMUGAVADIVU M,NAGARAJAN G,et al. Pharmalogical activities of antroquinonolmini review[J]. Chemico-Biological Interactions,2019,297:8-15.
[21] VILLAUME M T,SELLA E,SAUL G,et al. Antroquinonol A:scalable synthesis and preclinical biology of a phase 2drug candidate[J]. ACS Central Science,2016,2(1):27-31.
[22]夏永军,张贤芳,许赣荣.牛樟芝培养技术的研究进展[J].食品科学,2012,33(11):185-189.
[23] DORIYA K,JOSE N,GOWDA M,et al. Solid-state fermentation vs submerged fermentation for the production of L-asparaginase[J]. Advances in Food and Nutrition Research,2016,78:115-135.
[24]喻学淳,夏永军,张欢,等.樟芝固态发酵生产Antroquinonol及萃取Antroquinonl的研究[J].食品工业科技,2013,34(5):164-168.
[25]路瑞秋,胡永丹,张薄博,等.响应面法优化樟芝固态发酵产安卓奎诺尔[J].食品科学,2015,36(23):150-154.
[26] XIA Y J,WANG Y,HANG B B,et al. Effect of cultural conditions on antrodin C production by basidiomycete Antrodia camphorata in solid-state fermentation[J]. Biotechnology and Applied Biochemistry,2015,61(6):724-732.
[27] ABDULLAH B,MAFTUKHAH S,LISTYANINGRUM E,et al. In Effect of some variable in cellulase production by Aspergillus niger ITBCC L74 using solid state fermentation[C],Materials Science and Engineering Conference Series,2018.
[28] HANAI H,ISHIDA S,SAITO C,et al. Stimulation of mycelia growth in several mushroom species by rice husks[J]. Bioscience Biotechnology and Biochemistry,2005,69(1):123-127.
[29] SRIANTA I,ZUBAIDAH E,ESTIASIH T,et al. Comparison of Monascus purpureus growth,pigment production and composition on different cereal substrates with solid state fermentation[J]. Biocatalysis and Agricultural Biotechnology,2016,7:181-186.
[30] TAKESHITA R,SAIGUSA N,TREAMOTO Y. Production and antioxidant activity of alcoholic beverages made from various cereal grains using Monascus purpureus NBRC5965[J]. Journal of the Institute of Brewing,2016,122(2):350-354.
[31] YANGF C,YANGY H,LU H C. Enhanced antioxidant and antitumor activities of Antrodia cinnamomea cultured with cereal substrates in solid state fermentation[J]. Biochemical Engineering Journal,2013,78(37):108-113.
[32] TEREBIZNIK M R,PILOSOF A M R. Biomass estimation in solid state fermentation by modeling dry matter weight loss[J]. Biotechnology Techniques,1999,13(3):215-219.
[33] MAZAHERI D,SHOJAOSADATI S A,ZAMIR S M,et al.Mathematical modeling of ethanol production in solid-state fermentation based on solid medium dry weight variation[J]. Preparative Biochemistry and Biotechnology,2018,48(4):372-377.
[34]丁雪,马晓燕,张先舟,等.降解游离棉酚的热带假丝酵母菌的发酵动力学研究[J].中国酿造,2011,30(6):131-134.
[35]夏永军,李炜疆,许赣荣.樟芝固态发酵产品活性代谢产物分析[J].食品与发酵工业,2011,37(8):86-90.
[36]段传玲,兰静,张宏坤.分光光度法测定大米直链淀粉含量的误差分析[J].黑龙江农业科学,2015(4):129-133.
[37] WEUSTER B D. Experimental design for fermentation media development:statistical design or global random search[J]. Journal of Bioscience and Bioengineering,2000,90(5):473-483.
[38] RASHID S S,ALAM M Z,KARIM M I A,et al. Optimization of the nutrient supplients for cellulase production with the basal medium palm oil mill effluent[J]. World Academy of Science, Engineering and Technology,2009,60(6):809-815.
[39]吕腾飞,丁彦蕊,廖祥儒,等.竹黄菌固态发酵产竹红菌素条件的优化[J].食品与生物技术学报,2013,32(8):832-837.
[40]蔡一霞,朱智伟,王维,等.直链淀粉含量与稻米品质主要性状及米饭质地关系的研究[J].扬州大学学报(农业与生命科学版),2005,26(4):52-55.
[41]刘爱英,孙伟,梁宗琦,等.不同米质发酵生产红曲对莫纳可林K含量的影响[J].贵州农业科学,2003,31(5):5-7.
[42]冯杉,江林芡,李赛楠,等.无机盐和维生素对固体培养槐耳菌丝生长影响的研究[J].中南药学,2015,13(6):591-593.
[43]张帅,陈懿,董基,等.黑曲霉固态发酵橘皮生产纤维素酶及淀粉酶[J].食品科学,2012,33(11):190-193.
[44] LOTONG N,SUWANARIT P. Fermentation of ang-kak in plastic bags and regulation of pigmentation by initial moisture content[J]. Journal of Applied Microbiology,2010,68(6):565-570.
[45] LARROCHE C,THEODORE M,GROS J B. Growth and sporulation behaviour of Penicillium roquefortii in solid substrate fermentation:effect of the hydric parameters of the medium[J]. Applied Microbiology and Biotechnology,1992,38(2):183-187.
[46]童爱均,吕旭聪,刘晓艳,等.固体发酵基质和外加碳氮源对红曲霉色素产量的影响[J].中国调味品,2015(5):5-10.
[47]杨晓婉,张娜,李雪霞,等.大豆蛋白及其水解物在乳粉中的应用及研究进展[J].中国乳品工业,2018,46(4):31-34.
[48]陶红,梁歧,张鸣镝.热处理对大豆蛋白水解液分子量的影响[J].食品科学,2003,24(11):18-22.
[49] TANYILDIZI M S,ELIBBOL O M. Optimization ofα-amylase production by Bacillus sp. using response surface methodology[J]. Process Biochemical,2005,40(7):2 291-2 296.
[50]鞠兴荣,王雪峰,王立峰,等.混菌固态发酵菜籽粕制备菜籽肽的菌种筛选[J].食品与发酵工业,2011,37(9):104-108.