微生物合成血红蛋白的研究进展及其在食品中的应用Research Progress of Synthesis of Hemoglobin by Microorganisms and Its Application in Food
王庆沛,宇光海,廖爱美,潘龙,黄继红
摘要(Abstract):
血红蛋白是存在于原核和真核细胞中由血红素辅基和珠蛋白肽链构成的血红素蛋白,具有多种生理功能,常被用于医药与食品行业。在食品加工领域,其作为调味剂以提高代肉未来食品——植物蛋白肉的口感和拟真性可以满足有特殊营养要求的人们对肉类口感的需求。利用微生物发酵法生产血红蛋白相较于化学法提取具有操作方便、经济高效、环境友好等优势,近几年已经成为研究的热点。微生物高效表达血红蛋白的关键在于血红素的高水平供应与血红蛋白的正确表达两个方面,强化血红素合成途径、优化蛋白表达和发酵策略是实现血红蛋白高效表达的重要途径。文章围绕微生物高效合成血红蛋白最新研究进展、血红蛋白及其衍生物在食品中的应用开展综述,以期为促进微生物源血红蛋白在食品中的应用提供理论参考。
关键词(KeyWords): 血红蛋白;血红素;植物蛋白肉;未来食品;食品调味品
基金项目(Foundation): 河南省重大公益专项(201300110300);; 中原学者工作站资助项目(224400510026);; 河南省中央引导地方科技发展资金项目(Z20221341069);; 功能糖发酵菌株创制及绿色生物制造关键技术研究与应用(231111310700);; 河南省重大科技专项(221100110700)
作者(Author): 王庆沛,宇光海,廖爱美,潘龙,黄继红
参考文献(References):
- [1]NIEMI J K.Impacts of African swine fever on pigmeat markets in Europe[J].Frontiers in Veterinary Science,2020,7:634.
- [2]MCAULIFFE G A,TAKAHASHI T,LEE M R F.Framework for life cycle assessment of livestock production systems to account for the nutritional quality of final products[J].Food and Energy Security,2018,7(3):143.
- [3]GODDE C M,MASON-D'CROZ D,MAYBERRY D E,et al.Impacts of climate change on the livestock food supply chain;a review of the evidence[J].Global Food Security,2021,28:100488.
- [4]GIAMPIERO G,PIETRO G,ANDREA V,et al.Livestock and climate change:impact of livestock on climate and mitigation strategies[J].Animal Frontiers,2019,9(1):69-76.
- [5]李德茂,童胜,曾艳,等.未来食品的低碳生物制造[J].生物工程学报,2022,38(11):4311-4328.
- [6]李兆丰,孔昊存,刘延峰,等.未来食品:机遇与挑战[J].中国食品学报,2022,22(4):1-13.
- [7]GOLDSTEIN B,MOSES R,SAMMONS N,et al.Potential to curb the environmental burdens of American beef consumption using a novel plant-based beef substitute[J].PLoS One,2018,12(12):189029.
- [8]周景文,张国强,赵鑫锐,等.未来食品的发展:植物蛋白肉与细胞培养肉[J].食品与生物技术学报,2020,39(10):1-8.
- [9]LYU X Q,WU Y K,GONG M Y,et al.Synthetic biology for future food:research progress and future directions[J].Future Foods,2021,3:100025.
- [10]HERRERO M,THORNTON P K.Livestock and global change:emerging issues for sustainable food systems[J].Proceedings of the National Academy of Sciences of the United States of America,2013,110(52):20878-20881.
- [11]JIN Y,HE X,KWAME A K,et al.Evaluating potential risks of food allergy and toxicity of soy leghemoglobin expressed in Pichia pastoris[J].Molecular Nutrition & Food Research,2017,62(1):1700297.
- [12]ZHAO X R,ZHOU J W,DU G C,et al.Recent advances in the microbial synthesis of hemoglobin[J].Trends in Biotechnology,2020,39(3):286-297.
- [13]李冀宏,吕桂香,马宁,等.利用PyMol软件绘图辅助血红蛋白立体结构教学[J].生命的化学,2021,41(7):1417-1421.
- [14]李菂,韩樾夏,杨芳.血红蛋白氧载体的研究与应用进展[J].中国材料进展,2022,41(5):338-344.
- [15]曹艳丽,朱兵峰,时明星,等.透明颤菌血红蛋白的结构与功能及其在生物医药生产中的应用[J].中国医药工业杂志,2022,53(1):37-47.
- [16]薛志勇,代红生,张显元,等.表达透明颤菌血红蛋白基因对酿酒酵母生长及细胞内氧化状态的影响[J].中国生物工程杂志,2021,41(11):32-39.
- [17]王龙龙.豆血红蛋白调控根瘤高效固氮的分子机制研究[D].武汉:华中农业大学,2019.
- [18]赵亚兰,尉亚辉.豆血红蛋白的研究进展[J].西北植物学报,2000(4):684-689.
- [19]宋艳群,祝融峰,陈鹏.血红素的生理分布与调控[J].中国科学:化学,2015,45(11):1194-1205.
- [20]LEU B M,ZHANG Y,BU L,et al.Resilience of the iron environment in heme proteins[J].Biophysical Journal,2008,95(12):5874-5889.
- [21]YI Y C,SHIH I T,YU T H,et al.Challenges and opportunities of bioprocessing 5-aminolevulinic acid using genetic and metabolic engineering:a critical review[J].Bioresources and Bioprocessing,2021,8:100.
- [22]FRANKENBERG N,MOSER J,JAHN D.Bacterial heme biosynthesis and its biotechnological application[J].Applied Microbiology Biotechnology,2003,63(2):115-127.
- [23]LOU J W,ZHU L,WU M B,et al.High-level soluble expression of the hemA gene from Rhodobacter capsulatus and comparative study of its enzymatic properties[J].Journal of Zhejiang University:Science B,2014,15(5):491-499.
- [24]张俊丽,康振,钱晟东,等.产5-氨基乙酰丙酸酿酒酵母工程菌株的构建[J].食品与生物技术学报,2018,37(3):232-239.
- [25]HSUAN T,CHEN Y,TAI I,et al.Enhanced 5-aminolevulinic acid production by co-expression of codon-optimized hemA gene with chaperone in genetic engineered Escherichia coli[J].Applied Biochemistry and Biotechnology,2019,199(1):299-312.
- [26]RAAB A M,GEBHARDT G,BOLOTINA N,et al.Metabolic engineering of Saccharomyces cerevisiae for the biotechnological production of succinic acid[J].Metabolic Engineering,2010(6):12.
- [27]CHEN J,WANG Y,GUO X,et al.Efficient bioproduction of 5-aminolevulinic acid,a promising biostimulant and nutrient,from renewable bioresources by engineered Corynebacterium glutamicum[J].Biotechnology for Biofuels,2020,3(1):41.
- [28]REZAEI M N,ASLANKOOHI E,VERSTREPEN K J,et al.Contribution of the tricarboxylic acid (TCA) cycle and the glyoxylate shunt in Saccharomyces cerevisiae to succinic acid production during dough fermentation[J].International Journal of Food Microbiology,2015,204:24-32.
- [29]HARA K Y,MASARU S,HIROKO K,et al.5-Aminolevulinic acid fermentation using engineered Saccharomyces cerevisiae[J].Microbial Cell Factories,2019,18(1):194.
- [30]ZHU C,CHEN J,WANG Y,et al.Enhancing 5-aminolevulinic acid tolerance and production by engineering the antioxidant defense system of Escherichia coli[J].Biotechnology and Bioengineering,2019,116(8):2018-2028.
- [31]朱子薇.代谢工程改造解脂耶氏酵母生产5-氨基乙酰丙酸[D].济南:山东大学,2022.
- [32]KANG Z,ZHANG J,ZHOU J,et al.Recent advances in microbial production of δ-aminolevulinic acid and vitamin B12[J].Biotechnology Advances,2012,30(6):1533-1542.
- [33]朱子薇,张健,王倩,等.卟啉代谢途径高价值产物及其微生物合成研究进展[J].中国科学:生命科学,2020,50(12):1405-1417.
- [34]ZHANG S H,ZOU Y L,SONG X,et al.Advances in 5-aminolevulinic acid microbial production[J].Chinese Journal of Bioprocess Engineering,2017,15(5):65-70.
- [35]潘梅.大肠杆菌血红素合成调节及其对血红素过氧化物酶的影响[D].无锡:江南大学,2020.
- [36]PROTCHENKO O,PHILPOTT C C.Regulation of intracellular heme levels by HMX1,a homologue of heme oxygenase,in Saccharomyces cerevisiae[J].Journal of Biological Chemistry,2003,278(38):36582.
- [37]MARTíNEZ J L,PETRANOVIC D,NIELSEN J.Heme metabolism in stress regulation and protein production:from Cinderella to a key player[J].Bioengineered,2016,7(2):112-115.
- [38]KWON S J,DE BOER A L,PETRI R,et al.High-level production of porphyrins in metabolically engineered Escherichia coli:systematic extension of a pathway assembled from overexpressed genes involved in heme biosynthesis[J].Applied and Environmental Microbiology,2003,69(8):4875-4883.
- [39]ROK K C,EUN H Y,HOSEONG L,et al.Improved production of heme using metabolically engineered Escherichia coli[J].Biotechnology and Bioengineering,2022,119(11):3178-3193.
- [40]QIU Y Y,JUN T Z,YANG Y Z,et al.Microbial synthesis of heme b:biosynthetic pathways,current strategies,detection,and future prospects[J].Molecules,2023,28(8):3633.
- [41]ZHAO R X,CHOI R K,LEE Y S.Metabolic engineering of Escherichia coli for secretory production of free haem[J].Nature Catalysis,2018,1(9):720-728.
- [42]ZHANG J,LI Q,WANG Q,et al.Heme biosensor-guided in vivo pathway optimization and directed evolution for efficient biosynthesis of heme[J].Biotechnology for Biofuels and Bioproducts,2023,16(1):33.
- [43]HOFFMAN M,GóRA M,RYTKA J.Identification of rate-limiting steps in yeast heme biosynthesis[J].Biochemical Biophysical Research Communications,2003,310(4):1247-1253.
- [44]ISHCHUK O P,DOMENZAIN I,SáNCHEZ B J,et al.Genome-scale modeling drives 70-fold improvement of intracellular heme production in Saccharomyces cerevisiae[J].Proceedings of the National Academy of Sciences of the United States of America,2022,119(30):e2108245119.
- [45]DIETZ J V,WILLOUGHBY M M,PIEL R B,et al.Mitochondrial contact site and cristae organizing system (MICOS) machinery supports heme biosynthesis by enabling optimal performance of ferrochelatase[J].Redox Biology,2021,46(9):102125.
- [46]KO Y J,KIM M,YOU S K,et al.Animal-free heme production for artificial meat in Corynebacterium glutamicum via systems metabolic and membrane engineering[J].Metabolic Engineering,2021,66:217-228.
- [47]YANG S,WANG A,LI J,et al.Improved biosynthesis of heme in Bacillus subtilis through metabolic engineering assisted fed-batch fermentation[J].Microbial Cell Factories,2023,22(1):102.
- [48]PRANAWIDJAJA S,CHOI S I,LAY B W,et al.Analysis of heme biosynthetic pathways in a recombinant Escherichia coli[J].Journal of Microbiology & Biotechnology,2015,25(6):880-886.
- [49]陈丹园.大肠杆菌血红素合成途径关键酶基因的表达与调控[D].无锡:江南大学,2018.
- [50]LEE M J,CHUN S J,KIM H J,et al.Porphyrin derivatives from a recombinant Escherichia coli grown on chemically defined medium[J].Journal of Microbiology and Biotechnology,2012,22(12):1653-1658.
- [51]刘佳萌,李雪莹,刘业学,等.微生物以5-氨基乙酰丙酸为唯一前体物合成血红素的研究进展[J].中国生物工程杂志,2022,42(3):99-109.
- [52]HOFFMAN S J,LOOKER D L,ROEHRICH J M,et al.Expression of fully functional tetrameric human hemoglobin in Escherichia coli[J].Proceedings of the National Academy of Sciences,1990,87(21):8521-8525.
- [53]KERY V,ELLEDER D,KRAUS J P.Delta-aminolevulinate increases heme saturation and yield of human cystathionine beta-synthase expressed in Escherichia coli[J].Archives of Biochemistry & Biophysics,1995,316(1):24-29.
- [54]LIU L F,MARTíNEZ J L,LIU Z H,et al.Balanced globin protein expression and heme biosynthesis improve production of human hemoglobin in Saccharomyces cerevisiae[J].Metabolic Engineering,2014,21(1):9-16.
- [55]ISHCHUK O P,FROST A T,MUIZ-PAREDES F,et al.Improved production of human hemoglobin in yeast by engineering hemoglobin degradation[J].Metabolic Engineering,2021,66(3):259-267.
- [56]XUE J K,ZHOU J W,LI J H,et al.Systematic engineering of Saccharomyces cerevisiae for efficient synthesis of hemoglobins and myoglobins[J].Bioresource Technology,2022,370:128556.
- [57]ANWISED P,JANGPROMMA N,TEMSIRIPONG T,et al.Cloning,expression,and characterization of Siamese crocodile (Crocodylus siamensis) hemoglobin from Escherichia coli and Pichia pastoris[J].The Protein Journal,2016,35(4):256-268.
- [58]戎倩倩.产血红素和肌红蛋白酵母细胞工厂的构建及优化[D].北京:中国科学院大学,2021.
- [59]王紫微,赵鑫锐,周景文,等.一种高效合成血红素的毕赤酵母重组菌株的构建:中国,CN114874929A[P].2022-08-09.
- [60]ZHANG B H,ZHAO X R,WANG Z W,et al.Efficient secretory expression and purification of food-grade porcine myoglobin in Komagataella phaffii[J].Journal of Agricultural and Food Chemistry,2021,69(35):10235-10245.
- [61]张博涵.毕赤酵母组成型高效分泌合成猪肌红蛋白[D].无锡:江南大学,2022.
- [62]刘萌,王聪睿,刘波,等.豇豆血红蛋白Lb Ⅱ在大肠杆菌中的重组表达条件优化、纯化与鉴定[J].食品工业科技,2023,44(4):163-170.
- [63]苏悦.微生物高效表达异源豆血红蛋白的研究[D].杭州:浙江大学,2020.
- [64]SHAO Y R,XUE C L,LIU W Q,et al.High-level secretory production of leghemoglobin in Pichia pastoris through enhanced globin expression and heme biosynthesis[J].Bioresource Technology,2022,363:127884.
- [65]SUN F X,ZHAO Z Z ,WILLOUGHBY M M,et al.HRG-9 homologues regulate haem trafficking from haem-enriched compartments[J].Nature,2022,610(7933):768-774.
- [66]JOSé L M,LIU L,PETRANOVIC D,et al.Engineering the oxygen sensing regulation results in an enhanced recombinant human hemoglobin production by Saccharomyces cerevisiae[J].Biotechnology and Bioengineering,2015,112(1):181-188.
- [67]EJIMA D,WATANABE M,SATO Y,et al.High yield refolding and purification process for recombinant human interleukin-6 expressed in Escherichia coli[J].Biotechnology & Bioengineering,1999,62(3):301-310.
- [68]陈林杰,薛常鲁,苏悦,等.豆血红蛋白在毕赤酵母中的表达条件优化[J].微生物学通报,2022,49(6):2050-2061.
- [69]SANNY T,ARNALDOS M,KUNKEL S A,et al.Engineering of ethanolic E.coli with the Vitreoscilla hemoglobin gene enhances ethanol production from both glucose and xylose[J].Applied Microbiology & Biotechnology,2010,8(5):1103-1112.
- [70]张立娟,邢绍平,孔保华,等.糖基化血红蛋白着色剂在肉制品中的应用[J].肉类工业,2011(10):9-11.
- [71]张立娟,夏继华,沈峰,等.猪血血红蛋白肽的研究进展[J].肉类研究,2011,25(6):54-57.
- [72]宋璇,侯成立,高远,等.血红蛋白及其衍生物在食品中的应用[J].中国食品学报,2018,18(7):314-322.
- [73]徐兴达.酶解法改善猪血红蛋白的乳化性及其在烤肠中应用效果研究[D].郑州:河南农业大学,2014.
- [74]XING Y,GAO S,ZHANG X,et al.Dietary heme-containing proteins:structures,applications,and challenges[J].Foods,2022,11(22):3594.
- [75]汪学荣,王飞.生物态补铁剂——血红素铁的研究进展[J].中国食品添加剂,2007(3):82-87.
- [76]PAVAN K K,CHATLI M K,NITIN M,et al.Meat analogues:health promising sustainable meat substitutes[J].Critical Reviews in Food Science and Nutrition,2017,57(5):923-932.
- [77]ANNALISA G,FRANCESCA G,RACHELE G D,et al.The rise of processed meat alternatives:a narrative review of the manufacturing,composition,nutritional profile and health effects of newer sources of protein,and their place in healthier diets[J].Trends in Food Science & Technology,2022,127:263-271.
- [78]曾艳,郝学财,董婷,等.植物蛋白肉的原料开发、加工工艺与质构营养特性研究进展[J].食品工业科技,2021,42(3):338-345.
- [79]TIAN X W,LOVEDEEP K,YASUFUMI F,et al.3D printing of textured soft hybrid meat analogues[J].Foods,2022,11(3):478.