降脂红曲发酵工艺的研究进展
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摘要
降脂红曲是我国宝贵的药食同源发酵产品,其制曲菌种-红曲菌在发酵过程中能够产生具有降脂活性的次级代谢产物-莫纳可林K(Monacolin K)。对近年来降脂红曲的发展历史、红曲发酵的主要成分、Monacolin K的生物合成及降脂红曲的发酵工艺进行详细探究,对降脂红曲的未来发展方向提出了展望。旨在为后续有效提高红曲发酵Monacolin K产量提供参考。
Lipid-lowering red yeast rice is a valuable medicine and food homologous fermentation product in China. Its koji strain,Monascus,could produce a secondary metabolite Monacolin K with lipid-lowering activity during the fermentation process. The development history of lipid-lowering red yeast,the main components of red yeast fermentation,the biosynthesis of Monacolin K and the fermentation process of lipid-lowering red yeast had been explored in detail,and the future development direction of lipid-lowering red yeast was proposed. The aim was to provide a reference for the effective improvement of Monacolin K production of red yeast fermentation.
Lipid-lowering red yeast rice is a valuable medicine and food homologous fermentation product in China. Its koji strain,Monascus,could produce a secondary metabolite Monacolin K with lipid-lowering activity during the fermentation process. The development history of lipid-lowering red yeast,the main components of red yeast fermentation,the biosynthesis of Monacolin K and the fermentation process of lipid-lowering red yeast had been explored in detail,and the future development direction of lipid-lowering red yeast was proposed. The aim was to provide a reference for the effective improvement of Monacolin K production of red yeast fermentation.
引文
[1]Ajdari Z,Ghani M A,Ayob M K,et al.Hypocholesterolemic Activity of Monascus Fermented Product in the Absence of Monacolins with Partial Purification for Functional Food Applications[J].Scientific World Journal,2014,2014:1-2
[2]Perini M,Carbone G,Camin F.Stable isotope ratio analysis for authentication of red yeast rice[J].Talanta,2017,174:228-233
[3]Nigovi c B,Serti c M,Mornar A.Simultaneous determination of lovastatin and citrinin in red yeast rice supplements by micellar electrokinetic capillary chromatography[J].Food Chemistry,2013,138(1):531-538
[4]Mornar A,Serti c M,Nigovi c B.Development of a rapid LC/DAD/FLD/MS(n)method for the simultaneous determination of monacolins and citrinin in red fermented rice products[J].Journal of Agricultural&Food Chemistry,2013,61(5):1072-1080
[5]范颍磊,于游洋,曹云峰,等.辛伐他汀的合成研究新进展[J].山东化工,2016,45(14):45-47
[6]程文娟,杨大鹏,顾丰颖,等.微生物发酵产生他汀类化合物的研究进展[J].农产品加工(学刊),2011(2):76-80
[7]Chuang C Y,Shi Y C,You H P,et al.Antidepressant effect of GA-BA-rich monascus-fermented product on forced swimming rat model[J].Journal of Agricultural&Food Chemistry,2011,59(7):3027-3034
[8]Narsing Rao M P,Xiao M,Li W J.Fungal and Bacterial Pigments:Secondary Metabolites with Wide Applications[J].Front Microbiol,2017,8:1-4
[9]Cheng M J,Wu M D,Yuan G F,et al.Secondary metabolites produced by the fungus Monascus pilosus,and their anti-inflammatory activity[J].Phytochemistry Letters,2012,5(3):567-571
[10]Kim C,Jung H,Kim Y O,et al.Antimicrobial activities of amino acid derivatives of monascus pigments[J].Fems Microbiology Letters,2010,264(1):117-124
[11]吴铁,吕思敏,丁喜生,等.以红曲菌丝体为原料提取辅酶q10的工艺及生产方法:103613494 A[P].2014-03-05
[12]Manzoni M,Rollini M.Biosynthesis and biotechnological production of statins by filamentous fungi and application of these cholesterollowering drugs[J].Applied Microbiology&Biotechnology,2002,58(5):555-564
[13]Chen Y P,Tseng C P,Liaw L L,et al.Cloning and characterization of monacolin K biosynthetic gene cluster from Monascus pilosus[J].JAgric Food Chem,2008,56(14):5639-5646
[14]Sakai K,Kinoshita H,Nihira T.Identification of mokB,involved in monacolin K biosynthesis in Monascus pilosus[J].Biotechnology Letters,2009,31(12):1911-1916
[15]Chen Y P,Yuan G F,Hsieh S Y,et al.Identification of the mokHGene Encoding Transcription Factor for the Upregulation of Monacolin K Biosynthesis in Monascus pilosus[J].Journal of Agricultural&Food Chemistry,2010,58(1):287-293
[16]Dikshit R,Tallapragada P.Bio-synthesis and screening of nutrients for lovastatin by Monascus sp.under solid-state fermentation[J].Journal of Food Science&Technology,2015,52(10):6679-6686
[17]Panda B P,Javed S,Ali M.Production of angkak through co-culture of Monascus purpureus and Monascus ruber[J].Brazilian Journal of Microbiology,2010,41(3):757-764
[18]Suh S H,Rheem S,Mah J H,et al.Optimization of production of monacolin K from gamma-irradiated Monascus mutant by use of response surface methodology.[J].Journal of Medicinal Food,2007,10(3):408-415
[19]李桂杭,朱碧云,李浩明.土曲霉与红曲霉双灭活原生质体融合选育洛伐他汀高产菌株[J].食品与生物技术学报,2012,31(2):77-82
[20]Zhang B B,Lu L P,Xu G R.Why solid-state fermentation is more advantageous over submerged fermentation for converting high concentration of glycerol into Monacolin K by Monascus purpureus,9901:A mechanistic study[J].Journal of Biotechnology,2015,206:60-65
[21]许赣荣,胡文锋.固态发酵原理、设备与应用[M].北京:化学工业出版社,2009:42
[22]江利香,葛锋,刘畅.红曲洛伐他汀的高产策略[J].中草药,2011,42(7):1446-1452
[23]Lin T T.Production of the secondary metabolites gamma-aminobutyric acid and monacolin K by Monascus[J].J Ind Microbiol Biotechnol,2003,30(1):41-46
[24]Dikshit R,Tallapragada P.Statistical optimization of lovastatin and confirmation of nonexistence of citrinin under solid-state fermentation by Monascus sanguineus[J].Journal of Food&Drug Analysis,2016,24(2):433-440
[25]Lin L,Wang C,Li Z,et al.Effect of Temperature-Shift and Temperature-Constant Cultivation on the Monacolin K Biosynthetic Gene Cluster Expression in Monascus sp.[J].Food Technology and Biotechnology,2017,55(1):40-47
[26]Huang T,Tan H,Chen G,et al.Rising temperature stimulates the biosynthesis of water-soluble fluorescent yellow pigments and gene expression in Monascus ruber CGMCC10910[J].Amb Express,2017,7(1):134
[27]Chun-Lin Lee,Hsi-Kai Hung,Jyh-Jye Wang,et al.Improving the ratio of monacolin K to citrinin production of Monascus purpureus NTU 568 under dioscorea medium through the mediation of p H value and ethanol addition[J].Journal of Agricultural and Food Chemistry,2007,55(16):6493-6502
[28]Kang B,Zhang X,Wu Z,et al.Production of citrinin-free Monascus,pigments by submerged culture at low p H[J].Enzyme Microb Technol,2014,55(91):50-57
[29]Panda B P,Javed S,Ali M.Optimization of Fermentation Parameters for Higher Lovastatin Production in Red Mold Rice through Co-culture of Monascus purpureus,and Monascus ruber[J].Food&Bioprocess Technology,2010,3(3):373-378
[30]Chen F,Hu X.Study on red fermented rice with high concentration of monacolin K and low concentration of citrinin[J].International Journal of Food Microbiology,2005,103(3):331-337
[31]Lu L P,Zhang B B,Xu G R.Efficient conversion of high concentration of glycerol to Monacolin K by solid-state fermentation of Monascus purpureus using bagasse as carrier[J].Bioprocess&Biosystems Engineering,2013,36(3):293-299
[32]Atli B,YamaM,Yildiz Z,et al.Enhanced production of lovastatin by Omphalotus olearius(DC.)Singer in solid state fermentation.[J].Revista Iberoamericana De Micología,2015,32(4):247-251
[33]Pattanagul P,Pinthong R,Phianmongkhol A,et al.Mevinolin,citrinin and pigments of adlay angkak fermented by Monascus sp.[J].International Journal of Food Microbiology,2008,126(1):20-23
[34]Jaivel N,Marimuthu P.Optimization of lovastatin production in solid state fermentation by Aspergillus terreus[J].International Journal of Engineering Science&Technology,2010,2(7):2730-2733
[35]Javed S,Bukhari S A,Zovia I,et al.Screening of indigenously isolated fungi for lovastatin production and its in vivo evaluation[J].Current Pharmaceutical Biotechnology,2014,15(4):422-427
[36]Jirasatid S,Nopharatana M,Kitsubun P,et al.Statistical optimization for Monacolin K and yellow pigment production and citrinin reduction by Monascus purpureus in solid-state fermentation[J].Journal of Microbiology&Biotechnology,2013,23(3):364-374
[37]Zhang B B,Xing H B,Jiang B J,et al.Using millet as substrate for efficient production of monacolin K by solid-state fermentation of Monascus ruber[J].Journal of Bioscience&Bioengineering,2017,125(3):333-338
[38]Hsieh C W,Lu Y R,Lin S M,et al.Stability of monacolin K and citrinin and biochemical characterization of red-koji vinegar during fermentation[J].Journal of Agricultural&Food Chemistry,2013,61(30):7276-7283
[39]Huang T,Wang M,Shi K,et al.Metabolism and secretion of yellow pigment under high glucose stress with Monascus ruber[J].AMBExpress,2017,7(1):79
[40]Feng Y L,Shao Y C,Zhou Y X,et al.Effects of glycerol on pigments and monacolin K production by the high-monacolin K-producing but citrinin-free strain,Monascus pilosus MS-1[J].European Food Research&Technology,2015,240(3):635-643
[41]Seraman S,Rajendran A,Thangavelu V.Statistical optimization of anticholesterolemic drug lovastatin production by the red mold Monascus purpureus[J].Food&Bioproducts Processing,2010,88(2):266-276
[42]Chang Y N,Huang J C,Lee C C,et al.Use of response surface methodology to optimize culture medium for production of lovastatin by Monascus ruber[J].Enzyme&Microbial Technology,2002,30(7):889-894
[43]Sadik Ali Sayyad,Bibhu Prasad Panda,Saleem Javed,et al.Optimization of nutrient parameters for lovastatin production by Monascus purpureus,MTCC 369 under submerged fermentation using response surface methodology[J].Applied Microbiology and Biotechnology,2007,73(5):1054-1058
[44]Chan Z,Jian L,Le Y,et al.Glutamic acid promotes monacolin Kproduction and monacolin K biosynthetic gene cluster expression in Monascus[J].Amb Express,2017,7(1):22
[45]Zhang J,Wang Y L,Lu L P,et al.Enhanced production of Monacolin K by addition of precursors and surfactants in submerged fermentation of Monascus purpureus 9901[J].Biotechnol Appl Bioch-em,2014,61(2):202-207
[46]Huang J,Liao N,Li H.Linoleic Acid Enhance the Production of Moncolin K and Red Pigments in Monascus ruber by Activating mokH and mokA,and by Accelerating cAMP-PkA Pathway[J].International Journal of Biological Macromolecules,2017,109:950-954
[47]Wang J J,Lee C L,Pan T M.Improvement of monacolin K,γ-aminobutyric acid and citrinin production ratio as a function of environmental conditions of,Monascus purpureus,NTU 601[J].Journal of Industrial Microbiology&Biotechnology,2003,30(11):669-676
[48]Su Y C,Wang J J,Lin T T,et al.Production of secondary metabolites,γ-amino butyric acid and monacolin K by Monascus.J Ind Microbiol Biotechnol[J].Journal of Industrial Microbiology&Biotechnology,2003,30(1):41-46
[49]Kurokawa H,Ito H,Matsui H.Monascus purpureus induced apoptosis on gastric cancer cell by scavenging mitochondrial reactive oxygen species[J].Journal of Clinical Biochemistry&Nutrition,2017,61(3):189-195
[50]Hsu W H,Pan T M.Monascus purpureus-fermented products and oral cancer:a review[J].Applied Microbiology&Biotechnology,2012,93(5):1831-1842
[2]Perini M,Carbone G,Camin F.Stable isotope ratio analysis for authentication of red yeast rice[J].Talanta,2017,174:228-233
[3]Nigovi c B,Serti c M,Mornar A.Simultaneous determination of lovastatin and citrinin in red yeast rice supplements by micellar electrokinetic capillary chromatography[J].Food Chemistry,2013,138(1):531-538
[4]Mornar A,Serti c M,Nigovi c B.Development of a rapid LC/DAD/FLD/MS(n)method for the simultaneous determination of monacolins and citrinin in red fermented rice products[J].Journal of Agricultural&Food Chemistry,2013,61(5):1072-1080
[5]范颍磊,于游洋,曹云峰,等.辛伐他汀的合成研究新进展[J].山东化工,2016,45(14):45-47
[6]程文娟,杨大鹏,顾丰颖,等.微生物发酵产生他汀类化合物的研究进展[J].农产品加工(学刊),2011(2):76-80
[7]Chuang C Y,Shi Y C,You H P,et al.Antidepressant effect of GA-BA-rich monascus-fermented product on forced swimming rat model[J].Journal of Agricultural&Food Chemistry,2011,59(7):3027-3034
[8]Narsing Rao M P,Xiao M,Li W J.Fungal and Bacterial Pigments:Secondary Metabolites with Wide Applications[J].Front Microbiol,2017,8:1-4
[9]Cheng M J,Wu M D,Yuan G F,et al.Secondary metabolites produced by the fungus Monascus pilosus,and their anti-inflammatory activity[J].Phytochemistry Letters,2012,5(3):567-571
[10]Kim C,Jung H,Kim Y O,et al.Antimicrobial activities of amino acid derivatives of monascus pigments[J].Fems Microbiology Letters,2010,264(1):117-124
[11]吴铁,吕思敏,丁喜生,等.以红曲菌丝体为原料提取辅酶q10的工艺及生产方法:103613494 A[P].2014-03-05
[12]Manzoni M,Rollini M.Biosynthesis and biotechnological production of statins by filamentous fungi and application of these cholesterollowering drugs[J].Applied Microbiology&Biotechnology,2002,58(5):555-564
[13]Chen Y P,Tseng C P,Liaw L L,et al.Cloning and characterization of monacolin K biosynthetic gene cluster from Monascus pilosus[J].JAgric Food Chem,2008,56(14):5639-5646
[14]Sakai K,Kinoshita H,Nihira T.Identification of mokB,involved in monacolin K biosynthesis in Monascus pilosus[J].Biotechnology Letters,2009,31(12):1911-1916
[15]Chen Y P,Yuan G F,Hsieh S Y,et al.Identification of the mokHGene Encoding Transcription Factor for the Upregulation of Monacolin K Biosynthesis in Monascus pilosus[J].Journal of Agricultural&Food Chemistry,2010,58(1):287-293
[16]Dikshit R,Tallapragada P.Bio-synthesis and screening of nutrients for lovastatin by Monascus sp.under solid-state fermentation[J].Journal of Food Science&Technology,2015,52(10):6679-6686
[17]Panda B P,Javed S,Ali M.Production of angkak through co-culture of Monascus purpureus and Monascus ruber[J].Brazilian Journal of Microbiology,2010,41(3):757-764
[18]Suh S H,Rheem S,Mah J H,et al.Optimization of production of monacolin K from gamma-irradiated Monascus mutant by use of response surface methodology.[J].Journal of Medicinal Food,2007,10(3):408-415
[19]李桂杭,朱碧云,李浩明.土曲霉与红曲霉双灭活原生质体融合选育洛伐他汀高产菌株[J].食品与生物技术学报,2012,31(2):77-82
[20]Zhang B B,Lu L P,Xu G R.Why solid-state fermentation is more advantageous over submerged fermentation for converting high concentration of glycerol into Monacolin K by Monascus purpureus,9901:A mechanistic study[J].Journal of Biotechnology,2015,206:60-65
[21]许赣荣,胡文锋.固态发酵原理、设备与应用[M].北京:化学工业出版社,2009:42
[22]江利香,葛锋,刘畅.红曲洛伐他汀的高产策略[J].中草药,2011,42(7):1446-1452
[23]Lin T T.Production of the secondary metabolites gamma-aminobutyric acid and monacolin K by Monascus[J].J Ind Microbiol Biotechnol,2003,30(1):41-46
[24]Dikshit R,Tallapragada P.Statistical optimization of lovastatin and confirmation of nonexistence of citrinin under solid-state fermentation by Monascus sanguineus[J].Journal of Food&Drug Analysis,2016,24(2):433-440
[25]Lin L,Wang C,Li Z,et al.Effect of Temperature-Shift and Temperature-Constant Cultivation on the Monacolin K Biosynthetic Gene Cluster Expression in Monascus sp.[J].Food Technology and Biotechnology,2017,55(1):40-47
[26]Huang T,Tan H,Chen G,et al.Rising temperature stimulates the biosynthesis of water-soluble fluorescent yellow pigments and gene expression in Monascus ruber CGMCC10910[J].Amb Express,2017,7(1):134
[27]Chun-Lin Lee,Hsi-Kai Hung,Jyh-Jye Wang,et al.Improving the ratio of monacolin K to citrinin production of Monascus purpureus NTU 568 under dioscorea medium through the mediation of p H value and ethanol addition[J].Journal of Agricultural and Food Chemistry,2007,55(16):6493-6502
[28]Kang B,Zhang X,Wu Z,et al.Production of citrinin-free Monascus,pigments by submerged culture at low p H[J].Enzyme Microb Technol,2014,55(91):50-57
[29]Panda B P,Javed S,Ali M.Optimization of Fermentation Parameters for Higher Lovastatin Production in Red Mold Rice through Co-culture of Monascus purpureus,and Monascus ruber[J].Food&Bioprocess Technology,2010,3(3):373-378
[30]Chen F,Hu X.Study on red fermented rice with high concentration of monacolin K and low concentration of citrinin[J].International Journal of Food Microbiology,2005,103(3):331-337
[31]Lu L P,Zhang B B,Xu G R.Efficient conversion of high concentration of glycerol to Monacolin K by solid-state fermentation of Monascus purpureus using bagasse as carrier[J].Bioprocess&Biosystems Engineering,2013,36(3):293-299
[32]Atli B,YamaM,Yildiz Z,et al.Enhanced production of lovastatin by Omphalotus olearius(DC.)Singer in solid state fermentation.[J].Revista Iberoamericana De Micología,2015,32(4):247-251
[33]Pattanagul P,Pinthong R,Phianmongkhol A,et al.Mevinolin,citrinin and pigments of adlay angkak fermented by Monascus sp.[J].International Journal of Food Microbiology,2008,126(1):20-23
[34]Jaivel N,Marimuthu P.Optimization of lovastatin production in solid state fermentation by Aspergillus terreus[J].International Journal of Engineering Science&Technology,2010,2(7):2730-2733
[35]Javed S,Bukhari S A,Zovia I,et al.Screening of indigenously isolated fungi for lovastatin production and its in vivo evaluation[J].Current Pharmaceutical Biotechnology,2014,15(4):422-427
[36]Jirasatid S,Nopharatana M,Kitsubun P,et al.Statistical optimization for Monacolin K and yellow pigment production and citrinin reduction by Monascus purpureus in solid-state fermentation[J].Journal of Microbiology&Biotechnology,2013,23(3):364-374
[37]Zhang B B,Xing H B,Jiang B J,et al.Using millet as substrate for efficient production of monacolin K by solid-state fermentation of Monascus ruber[J].Journal of Bioscience&Bioengineering,2017,125(3):333-338
[38]Hsieh C W,Lu Y R,Lin S M,et al.Stability of monacolin K and citrinin and biochemical characterization of red-koji vinegar during fermentation[J].Journal of Agricultural&Food Chemistry,2013,61(30):7276-7283
[39]Huang T,Wang M,Shi K,et al.Metabolism and secretion of yellow pigment under high glucose stress with Monascus ruber[J].AMBExpress,2017,7(1):79
[40]Feng Y L,Shao Y C,Zhou Y X,et al.Effects of glycerol on pigments and monacolin K production by the high-monacolin K-producing but citrinin-free strain,Monascus pilosus MS-1[J].European Food Research&Technology,2015,240(3):635-643
[41]Seraman S,Rajendran A,Thangavelu V.Statistical optimization of anticholesterolemic drug lovastatin production by the red mold Monascus purpureus[J].Food&Bioproducts Processing,2010,88(2):266-276
[42]Chang Y N,Huang J C,Lee C C,et al.Use of response surface methodology to optimize culture medium for production of lovastatin by Monascus ruber[J].Enzyme&Microbial Technology,2002,30(7):889-894
[43]Sadik Ali Sayyad,Bibhu Prasad Panda,Saleem Javed,et al.Optimization of nutrient parameters for lovastatin production by Monascus purpureus,MTCC 369 under submerged fermentation using response surface methodology[J].Applied Microbiology and Biotechnology,2007,73(5):1054-1058
[44]Chan Z,Jian L,Le Y,et al.Glutamic acid promotes monacolin Kproduction and monacolin K biosynthetic gene cluster expression in Monascus[J].Amb Express,2017,7(1):22
[45]Zhang J,Wang Y L,Lu L P,et al.Enhanced production of Monacolin K by addition of precursors and surfactants in submerged fermentation of Monascus purpureus 9901[J].Biotechnol Appl Bioch-em,2014,61(2):202-207
[46]Huang J,Liao N,Li H.Linoleic Acid Enhance the Production of Moncolin K and Red Pigments in Monascus ruber by Activating mokH and mokA,and by Accelerating cAMP-PkA Pathway[J].International Journal of Biological Macromolecules,2017,109:950-954
[47]Wang J J,Lee C L,Pan T M.Improvement of monacolin K,γ-aminobutyric acid and citrinin production ratio as a function of environmental conditions of,Monascus purpureus,NTU 601[J].Journal of Industrial Microbiology&Biotechnology,2003,30(11):669-676
[48]Su Y C,Wang J J,Lin T T,et al.Production of secondary metabolites,γ-amino butyric acid and monacolin K by Monascus.J Ind Microbiol Biotechnol[J].Journal of Industrial Microbiology&Biotechnology,2003,30(1):41-46
[49]Kurokawa H,Ito H,Matsui H.Monascus purpureus induced apoptosis on gastric cancer cell by scavenging mitochondrial reactive oxygen species[J].Journal of Clinical Biochemistry&Nutrition,2017,61(3):189-195
[50]Hsu W H,Pan T M.Monascus purpureus-fermented products and oral cancer:a review[J].Applied Microbiology&Biotechnology,2012,93(5):1831-1842