Please wait a minute...

中国生物工程杂志

CHINA BIOTECHNOLOGY
中国生物工程杂志
中国生物工程杂志  2023, Vol. 43 Issue (1): 104-114    DOI: 10.13523/j.cb.2205015
综述     
甜菊糖苷的应用及生物合成研究进展*
李亚桐1,马媛媛2,3,**(),汪振洋4,宋浩1,5,**()
1 天津大学化工学院 天津 300072
2 天津大学海洋科学与技术学院 天津 300072
3 天津大学石油化工技术开发中心 天津 300072
4 中化健康产业发展有限公司 青岛 266071
5 天津大学(青岛)海洋工程研究院有限公司 青岛 266237
Research Progress of Application and Biosynthesis of Steviol Glycosides
LI Ya-tong1,MA Yuan-yuan2,3,**(),WANG Zhen-yang4,SONG Hao1,5,**()
1 School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China
2 School of Marine Science and Technology, Tianjin University, Tianjin 300072, China
3 Tianjin R&D Center for Petrochemical Technology, Tianjin University, Tianjin 300072, China
4 R&D Division, Sinochem Health Company Ltd., Qingdao 266071, China
5 Qingdao Institute of Ocean Engineering of Tianjin University Ltd., Qingdao 266237, China
 全文: PDF(2517 KB)   HTML
摘要：

甜菊糖苷是一种从甜叶菊叶片中提取的高甜度、零热量甜味剂,可用作食品添加剂。近年来,甜菊糖苷在国内外市场需求量剧增,引起了广泛关注。概述国际上对甜菊糖苷的安全性研究及评价,从经济价值角度分析甜菊糖苷的市场需求及应用前景,总结甜菊糖苷作为食品甜味添加剂的应用以及其在抗糖尿病、抗心脏纤维化、抗菌等保健功能方面的最新研究成果。综述甜菊糖苷的生物合成研究进展,重点介绍甜菊糖苷的微生物体从头合成以及生物催化低甜度糖苷生成高甜度、口感更优的甜菊糖苷,探讨提高甜菊糖苷产量的关键因素,为高端甜味剂绿色合成工艺的研究与开发提供理论依据。
关键词： 甜菊糖苷;  甜味剂;  莱胞迪苷D;  莱胞迪苷M;  生物合成    
Abstract:

Steviol glycosides are high-sweetness and zero-calorie sweeteners extracted from Stevia leaves. They can be used as food additives, and their demand in domestic and foreign markets has increased sharply, drawing widespread attention. The review discusses the safety research and evaluation of steviol glycosides in the world and analyzes the market demand and prospects of steviol glycosides from the perspective of economic value. Then, it summarizes the application of steviol glycosides as a sweetener in food and the latest research results in their anti-diabetic, anti-cardiac fibrosis, anti-bacterial and other health-care functions. The research progress in the production, preparation and biosynthesis of steviol glycosides is reviewed, with an emphasis on their de novo synthesis in microorganisms, and the latest progress in the biocatalytic conversion of low-sweet glycosides to produce steviol glycosides with higher sweetness and better taste. Finally, several key strategies for improving production of steviol glycosides are mentioned, and their future development prospects are discussed, providing a theoretical basis for the research and development of green synthesis process of high-end sweeteners.
Key words: Steviol glycosides    Sweeteners    Rebaudioside D    Rebaudioside M    Biosynthesis
收稿日期: 2022-05-06 出版日期: 2023-02-14
ZTFLH:  Q819  
基金资助: *天津市自然科学基金(18JCYBIC24200)
通讯作者: **马媛媛 电子信箱:myy@tju.edu.cn;宋浩 hsong@tju.edu.cn   
服务　　
把本文推荐给朋友
加入引用管理器
E-mail Alert
RSS
作者相关文章　　
李亚桐
马媛媛
汪振洋
宋浩

引用本文:

李亚桐, 马媛媛, 汪振洋, 宋浩. 甜菊糖苷的应用及生物合成研究进展*[J]. 中国生物工程杂志, 2023, 43(1): 104-114.

LI Ya-tong, MA Yuan-yuan, WANG Zhen-yang, SONG Hao. Research Progress of Application and Biosynthesis of Steviol Glycosides. China Biotechnology, 2023, 43(1): 104-114.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/10.13523/j.cb.2205015    或    https://manu60.magtech.com.cn/biotech/CN/Y2023/V43/I1/104

图1  甜叶菊中甜菊糖苷的合成路径[9]
图2  以UDP和蔗糖为糖基供体合成Reb A[58]
图3  “一锅法”生产Reb D[65]
图4  共固定化酶催化生成Reb D和Reb M[63]
[1] Mojto V, Singh R B, Gvozdjakova A, et al. The role of functional food security in global health. New York: Academic Press, 2019: 287-299.
[2] Salehi B, López M D, Martínez-López S, et al. Stevia rebaudiana Bertoni bioactive effects: from in vivo to clinical trials towards future therapeutic approaches. Phytotherapy Research, 2019, 33(11): 2904-2917.
doi: 10.1002/ptr.6478
[3] Zhang S S, Yang Y S, Lyu C C, et al. Identification of the key residues of the uridine diphosphate glycosyltransferase 91D2 and its effect on the accumulation of steviol glycosides in Stevia rebaudiana. Journal of Agricultural and Food Chemistry, 2021, 69(6): 1852-1863.
doi: 10.1021/acs.jafc.0c07066
[4] Libik-Konieczny M, Michalec-Warzecha Ż, Dziurka M, et al. Steviol glycosides profile in Stevia rebaudiana Bertoni hairy roots cultured under oxidative stress-inducing conditions. Applied Microbiology and Biotechnology, 2020, 104(13): 5929-5941.
doi: 10.1007/s00253-020-10661-5 pmid: 32468157
[5] Das A, Golder A K, Das C. Enhanced extraction of rebaudioside-A: experimental, response surface optimization and prediction using artificial neural network. Industrial Crops and Products, 2015, 65: 415-421.
doi: 10.1016/j.indcrop.2014.11.006
[6] De S, Mondal S, Banerjee S. Stevioside:technology, applications and health. West Sussex: John Wiley & Sons, Inc., 2013: 45-50.
[7] Kurek J M, Krejpcio Z. The functional and health-promoting properties of Stevia rebaudiana Bertoni and its glycosides with special focus on the antidiabetic potential -a review. Journal of Functional Foods, 2019, 61: 103465.
doi: 10.1016/j.jff.2019.103465
[8] Castro-Muñoz R, Correa-Delgado M, Córdova-Almeida R, et al. Natural sweeteners: sources, extraction and current uses in foods and food industries. Food Chemistry, 2022, 370: 130991.
doi: 10.1016/j.foodchem.2021.130991
[9] Olsson K, Carlsen S, Semmler A, et al. Microbial production of next-generation Stevia sweeteners. Microbial Cell Factories, 2016, 15(1): 207.
pmid: 27923373
[10] Basharat S, Huang Z Y, Gong M Y, et al. A review on current conventional and biotechnical approaches to enhance biosynthesis of steviol glycosides in Stevia rebaudiana. Chinese Journal of Chemical Engineering, 2021, 30: 92-104.
doi: 10.1016/j.cjche.2020.10.018
[11] Chen L L, Sun P, Zhou F F, et al. Synthesis of rebaudioside D, using glycosyltransferase UGTSL2 and in situ UDP-glucose regeneration. Food Chemistry, 2018, 259: 286-291.
doi: 10.1016/j.foodchem.2018.03.126
[12] Abdel-Rahman A, Anyangwe N, Carlacci L, et al. The safety and regulation of natural products used as foods and food ingredients. Toxicological Sciences, 2011, 123(2): 333-348.
doi: 10.1093/toxsci/kfr198 pmid: 21821733
[13] Lemus-Mondaca R, Vega-Gálvez A, Zura-Bravo L, et al. Stevia rebaudiana Bertoni, source of a high-potency natural sweetener: a comprehensive review on the biochemical, nutritional and functional aspects. Food Chemistry, 2012, 132(3): 1121-1132.
doi: S0308-8146(11)01755-9 pmid: 29243591
[14] Zhang J W, Bell L N. Stability of the Stevia-derived sweetener rebaudioside A in solution as affected by ultraviolet light exposure. Journal of Food Science, 2017, 82(4): 897-903.
doi: 10.1111/1750-3841.13667
[15] EFSA Panel on Food Additives and Flavourings (FAF), Younes M, Aquilina G, et al. Safety of the proposed amendment of the specifications for steviol glycosides (E 960) as a food additive: rebaudioside M produced via enzyme-catalysed bioconversion of purified Stevia leaf extract. EFSA Journal, 2019, 17(10): e05867.
[16] Sharma S, Walia S, Singh B, et al. Comprehensive review on agro technologies of low-calorie natural sweetener Stevia (Stevia rebaudiana Bertoni): a boon to diabetic patients. Journal of the Science of Food and Agriculture, 2016, 96(6): 1867-1879.
doi: 10.1002/jsfa.7500
[17] 孙传范, 李进伟. 甜菊糖苷研究进展. 食品科学, 2010, 31(9): 338-340.
Sun C F, Li J W. Research progress on steviosides. Food Science, 2010, 31(9): 338-340.
[18] Ahmad J, Khan I, Blundell R, et al. Stevia rebaudiana Bertoni.: an updated review of its health benefits, industrial applications and safety. Trends in Food Science & Technology, 2020, 100: 177-189.
[19] Mahajan M, Anuradha, Pal P K. Attaining higher biomass and steviol glycosides yields of Stevia rebaudiana through adjustment of plant population and nitrogen rate. Industrial Crops and Products, 2021, 165: 113426.
doi: 10.1016/j.indcrop.2021.113426
[20] Ljaz M, Pirzada A M, Saqib M, et al. Stevia rebaudiana: an alternative sugar crop in Pakistan - a review. Journal of Medicinal and Spice Plants, 2015, 20(2): 88-96.
[21] Ashwell M. Stevia, nature’s zero-calorie sustainable sweetener: a new player in the fight against obesity. Nutrition Today, 2015, 50(3): 129-134.
doi: 10.1097/NT.0000000000000094
[22] 禹晓, 杨媚, 翟娅菲, 等. 甜菊糖苷在我国保健食品中的应用现状分析及思考. 食品研究与开发, 2018, 39(7): 215-220.
Yu X, Yang M, Zhai Y F, et al. Analysis and reflection on the application status of stevioside in Chinese health food. Food Research and Development, 2018, 39(7): 215-220.
[23] Ciriminna R, Meneguzzo F, Pecoraino M, et al. A bioeconomy perspective for natural sweetener Stevia. Biofuels, Bioproducts and Biorefining, 2019, 13(3): 445-452.
doi: 10.1002/bbb.1968
[24] Rivera-Avilez J A, Jarma-Orozco A, Pompelli M F. Stevia rebaudiana Bertoni: the interaction of night interruption on gas exchange, flowering delay, and steviol glycosides synthesis. Horticulturae, 2021, 7(12): 543.
doi: 10.3390/horticulturae7120543
[25] MarketsandMarkets. Stevia market by extract type (whole leaf, powdered, liquid), application (dairy, bakery & confectionery, tabletop sweeteners, beverages, convenience foods), form (dry, liquid), and region-global forecasts to 2022. [2022-04-29]. https://www.marketsandmarkets.com/Market-Reports/stevia-market-167065378.html.
[26] Reports and Data. Stevia market size, share, trends, by type (powder, liquid and leaf), by form (dry and liquid), by application (dairy, bakery & confectionery, tabletop sweeteners, food & beverages, convenience food, others) and by region forecast to 2030. [2022-04-29]. https://www.reportsanddata.com/report-detail/stevia-market/research-methodology.
[27] Góngora Salazar V A, Vázquez Encalada S, Corona Cruz A, et al. Stevia rebaudiana: a sweetener and potential bioactive ingredient in the development of functional cookies. Journal of Functional Foods, 2018, 44: 183-190.
doi: 10.1016/j.jff.2018.03.007
[28] Heyden T. How did stevia get mainstream. [2022-04-29]. https://www.bbc.com/news/magazine-22758059.
[29] 胡朝晖. 甜菊糖苷产品的生产、销售及未来发展趋势. 中国食品添加剂, 2014(5): 176-179.
Hu Z H. The production, market and future development of Stevia. China Food Additives, 2014(5): 176-179.
[30] 郭雪霞, 赵仁邦. 甜菊糖苷的保健功能及其在食品中的应用. 中国食物与营养, 2012, 18(1): 32-35.
Guo X X, Zhao R B. Health function of stevioside and its application in food. Food and Nutrition in China, 2012, 18(1): 32-35.
[31] Vigneshwari K, Manonmani K. Effect of sugar replacer (Stevia and maltitol) on quality characteristics of bread. Asian Journal of Dairy and Food Research, 2020, 39(2): 159-163.
[32] di Monaco R, Miele N A, Cabisidan E K, et al. Strategies to reduce sugars in food. Current Opinion in Food Science, 2018, 19: 92-97.
doi: 10.1016/j.cofs.2018.03.008
[33] Sutwal R, Dhankhar J, Kindu P, et al. Development of low calorie jam by replacement of sugar with natural sweetener Stevia. International Journal of Current Research and Review, 2019, 11(4): 9-16.
[34] Márquez C, Caballero B, Vanegas K, et al. Eeffect of noncaloric sweeteners on the development of blackberry (Rubus glaucus Benth) jam. Temas Agrarios, 2016, 21(2): 32-39.
doi: 10.21897/rta.v21i2.899
[35] 崔天佑, 刘明铎. 一种含有甜菊糖甙的糖果及其制作方法: 中国, CN101884360A. 2010-11-17[2022-04-29]. https://cprs.patentstar.com.cn/Search/Detail?ANE=9ICD9HIG9IAA5CDA5CCA5CDA9EFB9EIH9CID9DAB9CDF9EHH.
Cui T Y, Liu M D. A kind of candy containing stevioside and its preparation method: China, CN101884360A. 2010-11-17[2022-04-29]. https://cprs.patentstar.com.cn/Search/Detail?ANE=9ICD9HIG9IAA5CDA5CCA5CDA9EFB9EIH9CID9DAB9CDF9EHH.
[36] Shah A B, Jones G P, Vasiljevic T. Sucrose-free chocolate sweetened with Stevia rebaudiana extract and containing different bulking agents - effects on physicochemical and sensory properties. International Journal of Food Science & Technology, 2010, 45(7): 1426-1435.
[37] Choi S N, Lee K J, Joo M K, et al. Quality characteristics of radish pickles added with different amounts of Stevia leaf. Journal of the East Asian Society of Dietary Life, 2017, 27(3): 295-303.
doi: 10.17495/easdl.2017.6.27.3.295
[38] Zou X M, Tan Q W, Goh B H, et al. ‘Sweeter’ than its name: anti-inflammatory activities of Stevia rebaudiana. All Life, 2020, 13(1): 286-309.
doi: 10.1080/26895293.2020.1771434
[39] Myint K Z, Chen J M, Zhou Z Y, et al. Structural dependence of antidiabetic effect of steviol glycosides and their metabolites on streptozotocin-induced diabetic mice. Journal of the Science of Food and Agriculture, 2020, 100(10): 3841-3849.
doi: 10.1002/jsfa.10421 pmid: 32297310
[40] Jia C H, Zhang J Y, Shen W, et al. Attenuation of high-fat diet-induced fatty liver through PPARα activation by stevioside. Journal of Functional Foods, 2019, 57: 392-398.
doi: 10.1016/j.jff.2019.04.034
[41] Alavala S, Sangaraju R, Nalban N, et al. Stevioside, a diterpenoid glycoside, shows anti-inflammatory property against dextran sulphate sodium-induced ulcerative colitis in mice. European Journal of Pharmacology, 2019, 855: 192-201.
doi: S0014-2999(19)30319-X pmid: 31075241
[42] Alavala S, Nalban N, Sangaraju R, et al. Anti-inflammatory effect of stevioside abates Freund’s complete adjuvant (FCA)-induced adjuvant arthritis in rats. Inflammopharmacology, 2020, 28(6): 1579-1597.
doi: 10.1007/s10787-020-00736-0
[43] Wei F Y, Zhu H, Li N, et al. Stevioside activates AMPK to suppress inflammation in macrophages and protects mice from LPS-induced lethal shock. Molecules (Basel, Switzerland), 2021, 26(4): 858.
doi: 10.3390/molecules26040858
[44] Wang J, Shen W, Zhang J Y, et al. Stevioside attenuates isoproterenol-induced mouse myocardial fibrosis through inhibition of the myocardial NF-κB/TGF-β1/Smad signaling pathway. Food & Function, 2019, 10(2): 1179-1190.
[45] 郎青云, 李慧, 祝谢民, 等. 超声辅助纤维素酶提取甜菊糖及其抑菌活性研究. 安徽农学通报, 2019, 25(21): 30-35.
Lang Q Y, Li H, Zhu X M, et al. Studies on ultrasonic-assisted cellulase extraction of Stevia and its antibacterial properties. Anhui Agricultural Science Bulletin, 2019, 25(21): 30-35.
[46] Wang J, Yang H, Li Q Q, et al. Novel nanomicelles based on rebaudioside A: a potential nanoplatform for oral delivery of honokiol with enhanced oral bioavailability and antitumor activity. International Journal of Pharmaceutics, 2020, 590: 119899.
doi: 10.1016/j.ijpharm.2020.119899
[47] Bursa Kovačevi D, Barba F J, Granato D, et al. Pressurized hot water extraction (PHWE) for the green recovery of bioactive compounds and steviol glycosides from Stevia rebaudiana Bertoni leaves. Food Chemistry, 2018, 254: 150-157.
doi: 10.1016/j.foodchem.2018.01.192
[48] Jentzer J B, Alignan M, Vaca-Garcia C, et al. Response surface methodology to optimise accelerated solvent extraction of steviol glycosides from Stevia rebaudiana Bertoni leaves. Food Chemistry, 2015, 166: 561-567.
doi: 10.1016/j.foodchem.2014.06.078
[49] Yılmaz F M, Görgüç A, Uygun Ö, et al. Steviol glycosides and polyphenols extraction from Stevia rebaudiana Bertoni leaves using maceration, microwave-, and ultrasound-assisted techniques. Separation Science and Technology, 2021, 56(5): 936-948.
doi: 10.1080/01496395.2020.1743311
[50] Lv X H, Kuang P Q, Yuan Q P, et al. Preparative separation of steviol glycosides from Stevia rebaudiana bertoni by macroporous resin and preparative HPLC. Acta Chromatographica, 2014, 26(1): 123-135.
doi: 10.1556/AChrom.26.2014.1.10
[51] Ameer K, Bae S W, Jo Y, et al. Optimization of microwave-assisted extraction of total extract, stevioside and rebaudioside-A from Stevia rebaudiana (Bertoni) leaves, using response surface methodology (RSM) and artificial neural network (ANN) modelling. Food Chemistry, 2017, 229: 198-207.
doi: 10.1016/j.foodchem.2017.01.121
[52] Ameer K, Chun B S, Kwon J H. Optimization of supercritical fluid extraction of steviol glycosides and total phenolic content from Stevia rebaudiana (Bertoni) leaves using response surface methodology and artificial neural network modeling. Industrial Crops and Products, 2017, 109: 672-685.
doi: 10.1016/j.indcrop.2017.09.023
[53] Gasmalla M A A, Yang R J, Hua X. Extraction of rebaudioside-A by sonication from Stevia rebaudiana Bertoni leaf and decolorization of the extract by polymers. Journal of Food Science and Technology, 2015, 52(9): 5946-5953.
doi: 10.1007/s13197-015-1717-3
[54] Gallo M, Vitulano M, Andolfi A, et al. Rapid solid-liquid dynamic extraction (RSLDE): a new rapid and greener method for extracting two steviol glycosides (stevioside and rebaudioside A) from Stevia leaves. Plant Foods for Human Nutrition (Dordrecht, Netherlands), 2017, 72(2): 141-148.
doi: 10.1007/s11130-017-0598-1
[55] Brahmachari G, Mandal L C, Roy R, et al. Stevioside and related compounds - molecules of pharmaceutical promise: a critical overview. Archiv Der Pharmazie, 2011, 344(1): 5-19.
doi: 10.1002/ardp.201000181 pmid: 21213347
[56] Jackson A U, Tata A, Wu C P, et al. Direct analysis of Stevia leaves for diterpene glycosides by desorption electrospray ionization mass spectrometry. The Analyst, 2009, 134(5): 867-874.
doi: 10.1039/b823511b
[57] Humphrey T V, Richman A S, Menassa R, et al. Spatial organisation of four enzymes from Stevia rebaudiana that are involved in steviol glycoside synthesis. Plant Molecular Biology, 2006, 61(1-2): 47-62.
pmid: 16786291
[58] Wang Y, Chen L L, Li Y, et al. Efficient enzymatic production of rebaudioside A from stevioside. Bioscience, Biotechnology, and Biochemistry, 2016, 80(1): 67-73.
doi: 10.1080/09168451.2015.1072457
[59] Prakash I, DuBois G E, Clos J F, et al. Development of rebiana, a natural, non-caloric sweetener. Food and Chemical Toxicology, 2008, 46(7): S75-S82.
doi: 10.1016/j.fct.2008.05.004
[60] Richman A, Swanson A, Humphrey T, et al. Functional genomics uncovers three glucosyltransferases involved in the synthesis of the major sweet glucosides of Stevia rebaudiana. The Plant Journal, 2005, 41(1): 56-67.
doi: 10.1111/j.1365-313X.2004.02275.x
[61] Wang J F, Li S Y, Xiong Z Q, et al. Pathway mining-based integration of critical enzyme parts for de novo biosynthesis of steviolglycosides sweetener in Escherichia coli. Cell Research, 2016, 26(2): 258-261.
doi: 10.1038/cr.2015.111
[62] 王蓓蓓. 甜叶菊UGT76G1在毕赤酵母细胞的表面展示. 广州: 华南理工大学, 2014.
Wang B B. Cell-surface display of UGT76G1 from Stevia rebaudiana in Pichia pastoris. Guangzhou: South China University of Technology, 2014.
[63] Wang Z Y, Liu W B, Liu W, et al. Co-immobilized recombinant glycosyltransferases efficiently convert rebaudioside A to M in cascade. RSC Advances, 2021, 11(26): 15785-15794.
doi: 10.1039/d0ra10574k pmid: 35481200
[64] Chen L L, Cai R X, Weng J Y, et al. Production of rebaudioside D from stevioside using a UGTSL 2 Asn358Phe mutant in a multi-enzyme system. Microbial Biotechnology, 2020, 13(4): 974-983.
doi: 10.1111/1751-7915.13539
[65] Wang Z Y, Hong J F, Ma S Y, et al. Heterologous expression of EUGT11 from Oryza sativa in Pichia pastoris for highly efficient one-pot production of rebaudioside D from rebaudioside A. International Journal of Biological Macromolecules, 2020, 163: 1669-1676.
doi: 10.1016/j.ijbiomac.2020.09.132
[66] 马媛媛, 汪振洋, 来庆英, 等. 一种能够催化莱鲍迪苷A生成莱鲍迪苷D的糖基转移酶StUGT: 中国, CN202011548177.7. 2020-12-24[2022-04-29]. https://cprs.patentstar.com.cn/Search/Detail?ANE=9FGE9GDA9CID9ICB9HHG5EAA9IDHBGIA9ACB9HFEBGFABHEA.
Ma Y Y, Wang Z Y, Lai Q Y, et al. A glycosyltransferase StUGT capable of catalyzing rebaudioside A to rebaudioside D: China, CN202011548177.7. 2020-12-24[2022-04-29]. https://cprs.patentstar.com.cn/Search/Detail?ANE=9FGE9GDA9CID9ICB9HHG5EAA9IDHBGIA9ACB9HFEBGFABHEA.
[67] Shu W J, Zheng H C, Fu X P, et al. Enhanced heterologous production of glycosyltransferase UGT76G 1 by co-expression of endogenous prpD and malK in Escherichia coli and its transglycosylation application in production of rebaudioside. International Journal of Molecular Sciences, 2020, 21(16): 5752.
doi: 10.3390/ijms21165752
[68] Liu Z F, Li J X, Sun Y W, et al. Structural insights into the catalytic mechanism of a plant diterpene glycosyltransferase SrUGT76G1. Plant Communications, 2020, 1(1): 100004.
doi: 10.1016/j.xplc.2019.100004
[69] 马媛媛, 李亚桐, 魏晓珍, 等. 一种与特定短肽标签融合能高效催化Reb M生成的重组酶: 中国, CN202111481579.4. 2021-12-07[2022-04-29]. https://cprs.patentstar.com.cn/Search/Detail?ANE=9GIH5DCA9FHF9HDC9CIC9AIA9CDA9DDF9GEC9HAD9EBD9GBH.
Ma Y Y, Li Y T, Wei X Z, et al. A recombinase that can efficiently catalyze the generation of Reb M fused to a specific short peptide tag: China, CN202111481579.4. 2022-12-07[2022-04-29]. https://cprs.patentstar.com.cn/Search/Detail?ANE=9GIH5DCA9FHF9HDC9CIC9AIA9CDA9DDF9GEC9HAD9EBD9GBH.
[70] 张璟譞, 高兵兵, 何冰芳. 生物催化中的酶固定化研究进展. 生物加工过程, 2022, 20(1): 9-19, 40.
Zhang J X, Gao B B, He B F. Research progress of enzyme immobilized in biocatalysis. Chinese Journal of Bioprocess Engineering, 2022, 20(1): 9-19, 40.
[1] 卞一凡,刘姝晗,张贝萌,张玉龙,李辛桐,王鹏超. 微生物合成2-苯乙醇研究进展*[J]. 中国生物工程杂志, 2022, 42(8): 128-136.
[2] 王荣香,宋佳,孙博,闫雪,张万忠,赵晨. 香豆素类化合物功能及生物合成研究进展*[J]. 中国生物工程杂志, 2022, 42(12): 79-90.
[3] 李然,闫晓光,李伟国,梁冬梅,财音青格乐,乔建军. 高效合成倍半萜酿酒酵母的构建策略*[J]. 中国生物工程杂志, 2022, 42(1/2): 14-25.
[4] 戢传富,王璐,苟敏,宋文枫,夏子渊,汤岳琴. 黄原胶生物合成及分子调控*[J]. 中国生物工程杂志, 2022, 42(1/2): 46-57.
[5] 张恒,刘慧燕,潘琳,王红燕,李晓芳,王彤,方海田. 生物法合成γ-氨基丁酸的研究策略*[J]. 中国生物工程杂志, 2021, 41(8): 110-119.
[6] 苗轶男,李敬知,王帅,李春,王颖. 萜烯生物合成中关键酶的研究进展*[J]. 中国生物工程杂志, 2021, 41(6): 60-70.
[7] 李冰,张传波,宋凯,卢文玉. 生物合成稀有人参皂苷的研究进展*[J]. 中国生物工程杂志, 2021, 41(6): 71-88.
[8] 翟君叶,成旭,孙泽敏,李春,吕波. 毛蕊花糖苷的生物合成研究进展[J]. 中国生物工程杂志, 2021, 41(5): 94-104.
[9] 郭二鹏, 张建志, 司同. 羊毛硫肽的高通量工程改造方法新进展 *[J]. 中国生物工程杂志, 2021, 41(1): 30-41.
[10] 刘啸尘, 范代娣, 杨帆, 武占省. 人参皂苷化合物生物合成进展 *[J]. 中国生物工程杂志, 2021, 41(1): 80-93.
[11] 王光路, 王梦园, 周忆菲, 马科, 张帆, 杨雪鹏. 吡咯喹啉醌生物合成研究进展 *[J]. 中国生物工程杂志, 2021, 41(1): 103-113.
[12] 饶海密,梁冬梅,李伟国,乔建军,财音青格乐. 真菌芳香聚酮化合物的合成生物学研究进展*[J]. 中国生物工程杂志, 2020, 40(9): 52-61.
[13] 段海荣,魏赛金,黎循航. 铜绿假单胞菌中鼠李糖脂生物合成的研究进展*[J]. 中国生物工程杂志, 2020, 40(9): 43-51.
[14] 邓廷山,武国干,孙宇,唐雪明. 苯乳酸生物合成的研究进展*[J]. 中国生物工程杂志, 2020, 40(9): 62-68.
[15] 闫伟欢,黄统,洪解放,马媛媛. 丁醇在大肠杆菌中的生物合成研究进展*[J]. 中国生物工程杂志, 2020, 40(9): 69-76.
主管：中国科学院 　主办：中国科学院文献情报中心 　中国生物技术发展中心 　中国生物工程学会