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中国生物工程杂志

CHINA BIOTECHNOLOGY
中国生物工程杂志  2021, Vol. 41 Issue (1): 94-102    DOI: 10.13523/j.cb.2009022
综述     
阿维拉霉素生物合成研究进展 *
宇光海(),彭海芬,王翱宇
河南工业大学生物工程学院 郑州 450001
Research Progress of Avilamycin Biosynthesis
YU Guang-hai(),PENG Hai-fen,WANG Ao-yu
College of Bioengineering, Henan University of Technology, Zhengzhou 450001, China
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摘要:

阿维拉霉素是由绿色产色链霉菌生产的寡糖类抗生素,对革兰氏阳性致病菌具有极强抗性,是一种新型饲料添加剂,广泛应用于肉鸡、仔猪等畜禽养殖中。以阿维拉霉素最新国内外研究进展为基础,综述了阿维拉霉素的抑菌机制、结构改造、菌种选育及发酵优化等方面的研究进展,重点阐述了阿维拉霉素的生物合成基因簇、合成途径及生物合成转录调控机制,探讨了提高阿维拉霉素产量的基因工程改造策略,为阿维拉霉素高效合成及工业化高产工程菌株构建等相关研究提供一定的理论参考。

关键词: 阿维拉霉素合成途径合成调控机制产量提高策略    
Abstract:

Avilamycin, an oligosaccharide antibiotic with strong antibacterial effect to Gram-positive intestinal pathogenic bacteria, has been widely used in livestock and poultry breeding, such as broiler chickens and piglets, as a new type of feed additive. The antibacterial mechanism, structural modification, high yield strain breeding and fermentation optimization of avilamycin were briefly reviewed and the gene clusters, synthetic pathways and transcriptional regulation mechanisms of avilamycin were highlighted, based on research progress in the past five years, in this work. Further, the strategies of genetic engineering to improve the yield of avilamycin were discussed, which could provide some references for the efficient synthesis of avilamycin and the construction of industrial high-yielding engineered strains.

Key words: Avilamycin    Synthetic pathway    Synthesis regulation mechanism    Strategies to increase production
收稿日期: 2020-09-11 出版日期: 2021-02-09
ZTFLH:  Q819  
基金资助: * 国家自然科学基金(21506048)
通讯作者: 宇光海     E-mail: guanghaiyu66@haut.edu.cn
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引用本文:

宇光海, 彭海芬, 王翱宇. 阿维拉霉素生物合成研究进展 *[J]. 中国生物工程杂志, 2021, 41(1): 94-102.

YU Guang-hai, PENG Hai-fen, WANG Ao-yu. Research Progress of Avilamycin Biosynthesis. China Biotechnology, 2021, 41(1): 94-102.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/10.13523/j.cb.2009022        https://manu60.magtech.com.cn/biotech/CN/Y2021/V41/I1/94

图1  阿维拉霉素分子结构示意图[15]
图2  阿维拉霉素的作用机制[18]
开放阅读框序号 基因 可能编码的产物 推测的功能
20 aviN 酮酰合成酶III同源酶 合成苔色酸的起始单元
21 aviM I型聚酮合成酶 合成苔色酸
22 aviD dTDP-葡萄糖合成酶 残基B、C、D的合成起始酶
23, 48 aviE1, aviS dTDP-葡萄糖-4,6-脱水酶 参与残基B、C、D的合成
28 aviE2 UDP-葡萄糖醛酸脱羧酶 残基G的合成起始酶
47 aviE3 GDP-甘露糖-4,6-脱水酶 残基E的合成起始酶
37,38 aviB1, aviB2 丙酮酸脱氢酶(α链,β链) 参与残基H的合成
18 aviG1 甲基转移酶 残基G的结构修饰
25 aviG5 甲基转移酶 残基E的C-4位结构修饰
29, 31 aviG2, aviG6 甲基转移酶 残基F的C2、C6结构修饰
33 aviG3 甲基转移酶 参与残基H的结构修饰
46 aviG4 甲基转移酶 参与残基A的结构修饰
11, 24, 43 aviQ1, aviQ2, aviQ3 UDP-葡萄糖-4-差向异构酶 寡糖的差向异构
30 aviZ1 酮还原酶 参与残基D、E的合成
49 aviT 酮还原酶 参与残基B、C、D的合成
50 aviZ3 酮还原酶 参与残基B、C的合成
51 aviZ2 酮还原酶 参与残基D、E的合成
44 aviH 卤化酶 参与残基A的结构修饰
34 aviX12 S-腺苷甲硫氨酸酶 活化残基F-G
26, 32 aviO1, aviO3 羟化酶 原酸酯键及糖苷键的形成
41 aviO2 羟化酶 参与残基H的合成
27, 12, 39 aviGT1, aviGT2, aviGT3 糖基转移酶 七糖链的组装
40 aviGT4 糖基转移酶 连接残基G与残基H
14, 15 aviC1, aviC2 调控蛋白 途径特异性正向调控因子
6, 10 aviRa, aviRb rRNA甲基转移酶 与阿维拉霉素的抗性有关
35, 36 aviABC1, aviABC1 ABC转运蛋白,ATP结合蛋白 参与阿维拉霉素的转运
表1  阿维拉霉素合成基因簇中的主要功能基因
图3  阿维拉霉素生物合成基因簇[8]
图4  推测的阿维拉霉素A生物合成途径[8]
[1] 邹君彪, 姜平. 阿维拉霉素的研究进展. 国外畜牧学(猪与禽), 2017,37(10):94-97.
Zou J B, Jiang P. Research progress of avilamycin. Animal Science Abroad (Pigs and Poultry), 2017,37(10):94-97.
[2] Choi J H, Lee K, Kim D W, et al. Influence of dietary avilamycin on ileal and cecal microbiota in broiler chickens. Poultry Science, 2018,97(3):970-979.
pmid: 29253227
[3] 王东卫, 王瑛. 饲用抗生素在雏鸡生产中应用效果的比较. 饲料工业, 2011,32(24):62-64.
Wang D W, Wang Y. Comparison of application effect of feed antibiotics in chicken production. Feed Industry, 2011,32(24):62-64.
[4] 刘英杰. 互联网+鲤鱼使用抗生素对生长性能的研究. 农业工程技术, 2017,37(27):48-49.
Liu Y J. Effects of antibiotics on growth performance of carp. Agricultural Engineering Technology, 2017,37(27):48-49.
[5] Saito S S, Hayashi T, Nemoto S, et al. Determination of total avilamycin residues as dichloroisoeverninic acid in porcine muscle, fat, and liver by LC-MS/MS. Food Chemistry, 2018,249(12):84-90.
[6] Liu Y P. The effect of avialmycin on growth performance and body immune response of juvenile jian carp (Cyprinus Carpio Var. Jian). Ya’an: Sichuan Agricultural University, 2011.
[7] 王乙茹, 柳成东, 白华毅, 等. 凝结芽孢杆菌与饲用抗生素组合使用对21~42日龄AA肉鸡生产性能的影响. 中国畜牧杂志, 2019,55(12):123-126.
Wang Y R, Liu C D, Bai Y H, et al. Effects of Bacillus coagulans combined with antibiotics on the performance of AA Broilers aged 21~42 days. Chinese Journal of Animal Science, 2019,55(12):123-126.
[8] Weitnauer G, Muhlenweg A, Trefzer A, et al. Biosynthesis of the orthosomycin antibiotic avilamycin A: deductions from the molecular analysis of the avi biosynthetic gene cluster of Streptomyces viridochromogenes Tü57 and production of new antibiotics. Chemistry & Biology, 2001,8(6):569-581.
[9] 李政, 李燕, 陶兴无, 等. 阿维拉霉素产生菌的育种研究进展. 武汉工业学院学报, 2009,28(4):38-41.
Li Z, Li Y, Tao X W, et al. Advances of screening for high-yeild Avilamycin-producing strain. Journal of Wuhan Polytechnic University, 2009,28(4):38-41.
[10] 刘芳, 李晓荣, 邹祥. 阿维拉霉素高产菌株选育与发酵特性. 西南大学学报(自然科学版), 2012,34(11):143-148.
Liu F, Li X R, Zou X. Screening of a high-yield avilamycin-producing strain and its fermentation properties. Journal of Southwest University (Natural Science Edition), 2012,34(11):143-148.
[11] 任健, 童应凯, 吴兆亮. 卑霉素的合成途径及分子生物学进展. 天津农学院学报, 2008(3):47-51.
Ren J, Tong Y K, Wu Z L. Biosynthesis pathway and molecular biology progress of avilamycin. Journal of Tianjin Agricultural University, 2008(3):47-51.
[12] 潘镇涛, 林凌, 郑雪媚, 等. HPLC法测定阿维拉霉素预混剂中阿维拉霉素的含量. 安徽农学通报, 2017,23(12):157-159.
Pan Z T, Lin L, Zheng X M, et al. Determination of the content of avilamycin in 10% avilamycin premix by HPLC method. Anhui Agricultural Science Bulletin, 2017,23(12):157-159.
[13] 梁新乐, 张丹丹, 陈敏, 等. 阿维拉霉素高产菌株绿色产色链霉菌A11-13的推理选育. 中国抗生素杂志, 2012,37(9):671-677.
Liang X L, Zhang D D, Chen M, et al. Rational breeding of high avilamycin-producing strain of Streptomyces viridoehrongenes A11-13. Chinese Journal of Antibiotics, 2012,37(9):671-677.
[14] 闵江, 刘正光, 梁景乐, 等. 阿维拉霉素提取工艺的研究. 中国动物保健, 2017,19(11):75-78.
Min J, Liu Z G, Liang J L, et al. Study on extraction technology of avilamycin. China Animal Health, 2017,19(11):75-78.
[15] 刘芳, 李晓荣, 邹祥. 阿维拉霉素生物合成与代谢调控研究进展. 生物技术通报, 2010 (12):25-30.
Liu F, Li X R, Zou X. Advances on biosynthesis approach and metabolic regulation of avilamycin. Biotechnology Bulletin, 2010 (12):25-30.
[16] Arenz S, Juette M F, Graf M, et al. Structures of the orthosomycin antibiotics avilamycin and evernimicin in complex with the bacterial 70S ribosome. Proceedings of the National Academy of Sciences of the United States of America, 2016,113(27):7527-7532.
[17] Kofoed C B, Vester B. Interaction of avilamycin with ribosomes and resistance caused by mutations in 23S rRNA. Antimicrobial Agents and Chemotherapy, 2002,46(11):3339-3342.
[18] Aarestrup F M, Jensen L B. Presence of variations in ribosomal protein L16 corresponding to susceptibility of enterococci to oligosaccharides (avilamycin and evernimicin). Antimicrobial Agents and Chemotherapy, 2000,44(12):3425-3427.
[19] Krupkin M, Wekselman I, Matzov D, et al. Avilamycin and evernimicin induce structural changes in rProteins uL16 and CTC that enhance the inhibition of A-site tRNA binding. Proceedings of the National Academy of Sciences of the United States of America, 2016,113(44):E6796-E6805.
[20] Gaisser S, Tefzer A, Stockert S, et al. Cloning of an avilamycin biosynthetic gene cluster from Streptomyces viridochromogenes Tü57. Journal of Bacteriology, 1997,179(20):6271-6278.
[21] Weitnauer G, Muhlenweg A, Trefzer A, et al. An ATP-binding cassette transporter and two rRNA methyltransferases are involved in resistance to avilamycin in the producer organism Streptomyces viridochromogenes Tü57. Antimicrobial Agents and Chemotherapy, 2001,45(3):690-695.
[22] Hofmann C, Boll R, Heitmann B, et al. Genes encoding enzymes responsible for biosynthesis of L-lyxose and attachment of eurekanate during avilamycin biosynthesis. Chemistry & Biology, 2005,12(10):1137-1143.
pmid: 16242656
[23] Hyun C G, Kim S S, Sohng J K, et al. An efficient approach for cloning the dNDP-glucose synthase gene from actinomycetes and its application in Streptomyces spectabilis, a spectinomycin producer. FEMS Microbiology Letters, 2000,183(1):183-189.
pmid: 10650224
[24] Weitnauer G, Muhlenweg A, Trefzer A, et al. Analysis of a C-methyltransferase gene (aviG1) involved in avilamycin biosynthesis in Streptomyces viridochromogenes Tü57 and complementation of a Saccharopolyspora erythraea eryBIII mutant by aviG1. Microbiology, 2002,148(2):373-379.
[25] Yamauchi N, Kakinuma K. Enzymic carbocycle formation in microbial secondary metabolism. The mechanism of the 2-deoxy-scyllo-inosose synthase reaction as a crucial step in the 2-deoxystreptamine biosynthesis in Streptomyces fradiae. The Journal of Organic Chemistry, 2002,60(17):5614-5619.
[26] Schmidt M S, Wittmann V. Stereoselective synthesis of 1,1'-linked alpha-L-lyxopyranosyl beta-D-glucopyranoside, the proposed biosynthetic precursor of the FG ring system of avilamycins. Carbohydrate Research, 2008,343(10-11):1612-1623.
pmid: 18495098
[27] Treede I, Hauser G, Mühlenweg A, et al. Genes involved in formation and attachment of a two-carbon chain as a component of eurekanate, a branched-chain sugar moiety of avilamycin A. Applied and Environmental Microbiology, 2005,71(1):400-406.
[28] Trefzer A, Hoffmeister D, Künzel E, et al. Function of glycosyltransferase genes involved in urdamycin abiosynthesis. Chemistry & Biology, 2000,7(2):133-142.
[29] Martinez F C, Proctor M, Roberts S, et al. Insights into the synthesis of lipopolysaccharide and antibiotics through the structures of two retaining glycosyltransferases from family GT4. Chemistry & Biology, 2006,13(11):1143-1152.
[30] Stewart V, Chen L L, Wu H C. Response to culture aeration mediated by the nitrate and nitrite sensor NarQ of Escherichia coli K-12. Molecular Microbiology, 2003,50(4):1391-1399.
[31] Galperin M Y, Nikolskaya A N, Koonin E V. Novel domains of the prokaryotic two-component signal transduction systems. FEMS Microbiology Letters, 2001,203(1):11-21.
[32] Lin A V, Stewart V. Functional roles for the GerE-family carboxylterminal domains of nitrate response regulators NarL and NarP of Escherichia coli K-12. Microbiology, 2010,156(10):2933-2943.
[33] Rebets Y, Boll R J, Horbal L, et al. Production of avilamycin A is regulated by AviC1and AviC2, two transcriptional activators. The Journal of Antibioticst, 2009,62(8):461-464.
[34] Weitnauer G, Hauser G, Hofmann C, et al. Novel avilamycin derivatives with improved polarity generated by targeted gene disruption. Chemistry & Biology, 2004,11(10):1403-1411.
[35] 王亚萍, 陈敏, 李红梅. 硅胶对阿维拉霉素吸附特性的研究. 中国药学杂志, 2018,53(16):1388-1394.
Wang Y P, Chen M, Li H M. Adsorption property of avilamycin on silica gel-based absorbent. Chinese Pharmaceutical Journal, 2018,53(16):1388-1394.
[36] Cardinal K M, Kipper M, Andretta I, et al. Withdrawal of antibiotic growth promoters from broiler diets: performance indexes and economic impact. Poultry Science, 2019,98(12):6659-6667.
pmid: 31544941
[37] Boll R, Koslowski T, Hofmann C, et al. The active conformation of avilamycin A is conferred by AviX12, a radical AdoMet enzyme. The Journal of Biological Chemistry, 2006,281(21):14756-14763.
pmid: 16537546
[38] 刘芳. 阿维拉霉素菌种推理选育与aviD基因的强化表达研究. 重庆:西南大学, 2012.
Liu F. Rationally breeding and expression of aviD gene in Streptomyces viridochromogenes. Chongqing: Southwest University, 2012.
[39] 向荣华, 詹晓北, 朱莉, 等. 常压室温等离子体诱变绿色产色链霉菌及阿维拉霉素高产菌选育. 中国抗生素杂志, 2015,40(10):732-737.
Xiang R H, Zhan X B, Zhu L, et al. Screening of high yield avilamycin mutant of Streptomyces viridochromogene through atmospheric and room temperature plasma mutagenesis. Chinese Journal of Antibiotics, 2015,40(10):732-737.
[40] 赵硕珍, 张云峰, 姬胜利, 等. 阿维拉霉素高产菌株的选育. 中国生化药物杂志, 2008(4):256-259.
Zhao S Z, Zhang Y F, Ji S L, et al. Screening avilamycin-producing strain for high-yield. Chinese Journal of Biochemical Pharmaceuticals, 2008(4):256-259.
[41] 靳亮. 卑霉素产生菌的菌种选育和发酵工艺研究. 泰安:山东农业大学, 2006.
Jin L. Study on avilamycin rational screening and fermentation process optimization. Taian: Shandong Agricultural University, 2006.
[42] 胡奇杰. 阿维拉霉素生产菌推理选育及其发酵条件的初步研究. 杭州:浙江工商大学, 2007.
Hu Q J. Rationally breeding of avilamycin producing strains and optimlizing of conditions of fermentation. Hangzhou: Zhejiang Gongshang University, 2007.
[43] 刘华华, 陈宇航, 陈敏. 核糖体工程技术选育阿维拉霉素高产菌株. 农业生物技术学报, 2019,27(7):1322-1330.
Liu H H, Chen Y H, Chen M. Breeding of high avilamycin-producing strains by ribosome engineering. Journal of Agricultural Biotechnology, 2019,27(7):1322-1330.
[44] 王庆龄. 阿维拉霉素高产菌株选育. 杭州:浙江工商大学, 2015.
Wang Q L. Breeding high avilamycin-producers by Streptomyces viridochromogenes. Hangzhou: Zhejiang Gongshang University, 2015.
[45] Ega S L, Drendel G, Petrovski S, et al. Comparative analysis of structural variations due to genome shuffling of Bacillus Subtilis VS15 for improved cellulase production. International Journal of Molecular Sciences, 2020,21(4):1299-1301.
[46] Lv X A, Jin Y Y, Zhang H, et al. Genome shuffling of Streptomyces viridochromogenes for improved production of avilamycin. Applied Microbiology and Biotechnology, 2013,97(2):641-648.
[47] 张丹丹. 阿维拉霉素产生菌的定向育种及机制研究. 杭州:浙江工商大学, 2012.
Zhang D D. Rational breeding high avilamycin-producers in Streptomyces viridochromogenes and deciphering its evolution mechansim. Hangzhou: Zhejiang Gongshang University, 2012.
[48] 毛灵琪, 李存治, 陶兴无, 等. 利用基因组改组技术选育阿维拉霉素高产菌. 生物技术通报, 2015,31(5):54-60.
Mao Q L, Li C Z, Tao X W, et al. Screening and breeding strains producing high-yield avilamycin by genome shuffling. Biotechnology Bulletin, 2015,31(5):54-60.
[49] 李红梅, 陈敏. 响应面优化绿色产色链霉菌发酵产阿维拉霉素. 中国食品学报, 2017,17(9):108-115.
Li H M, Chen M. Fermentation optimization of avilamycin using Streptomyces viridochromogenes by response surface methodology. Journal of Chinese Institute of Food Science and Technology, 2017,17(9):108-115.
[50] 靳亮, 王泽立, 童应凯, 等. 响应面法优化卑霉素发酵培养基的研究. 生物技术通报, 2007(2):155-158,162.
Jin L, Wang Z L, Dong Y K, et al. Response surface methdology for optimizing avilamycin fermentation medium. Biotechnology Bulletin, 2007(2):155-158,162.
[51] Zhu C H, Lu F P, He Y N, et al. Statistical optimization of medium components for avilamycin production by Streptomyces viridochromogenes Tü57-1 using response surface methodology. Journal of Industrial Microbiology & Biotechnology, 2007,34(4):271-278.
pmid: 17186208
[52] 张善飞, 王丹丹, 关志勇. 阿维拉霉素发酵条件的研究. 粮食与饲料工业, 2015(11):58-60,69.
Zhang S F, Wang D D, Guan Z Y. Fermentation conditions of avilamycin. Cereal & Feed Industry, 2015(11):58-60,69.
[53] 陈永辉, 刘波, 曾兆国, 等. 阿维拉霉素的研究进展. 饲料工业, 2007(14):9-11.
Chen Y H, Liu B, Zeng Z G, et al. Research progress of avilamycin. Feed Industry, 2007(14):9-11.
[54] 李国栋. 阿维拉霉素生产菌诱变育种及发酵工艺优化. 天津:天津大学, 2011.
Li G D. Mutation inducing breeding of avilamycins production and optimization of fermentation conditions. Tianjin: Tianjin University, 2011.
[55] 章梅, 宋元达, 刘青, 等. 氧载体对绿色产色链霉菌发酵生产阿维拉霉素的影响. 食品与机械, 2018,34(2):42-45,128.
Zhang M, Song Y D, Liu Q, et al. Effect of oxygen carrier on the production of avilamycin by Streptomyces chromogenes. Food & Machinery, 2018,34(2):42-45,128.
[56] 潜媛媛, 陈敏, 王宏. 分段调控优化阿维拉霉素生产菌罐上发酵参数. 食品与机械, 2013,29(1):27-30,56.
Qian Y Y, Chen M, Wang H. Optimization of fermentation parameters of avilamycin producing strain by segmented regulation. Food & Machinery, 2013,29(1):27-30,56.
[57] 朱传合, 贺亚男, 路福平, 等. 微波对阿维拉霉素产生菌诱变效应的研究. 现代生物医学进展, 2006(4):32-34.
Zhu C H, He Y N, Lu F P, et al. A study on mutagenic effects of avilamycin-producing strain induced by microwave irradiation. Progress in Modern Biomedicine, 2006(4):32-34.
[58] 胡向东, 冯云会, 叶茂, 等. 随机诱变和基因组重排选育阿维拉霉素高产菌. 食品与发酵工业, 2019,45(7):1-7.
Hu X D, Feng Y H, Ye M, et al. Random mutagenesis and genome shuffling screen Streptomyces viridoehrongenes producing high-yield avilamycin. Food and Fermentation Industries, 2019,45(7):1-7.
[59] 任健, 童应凯, 王俊斌, 等. 卑霉素产生菌Tü-57的诱变育种研究. 安徽农业科学, 2012,40(4):1939-1940,2066.
Ren J, Tong Y K, Wang J B, et al. Study of high avilamycin-producing strains Tü-57’s by combined mutagenic agents. Journal of Anhui Agricultural Sciences, 2012(4):1939-1940,2066.
[60] 王园园, 王康, 金令凯, 等. 阿维拉霉素发酵工艺优化及动力学模型建立. 高校化学工程学报, 2019,33(5):1156-1163.
Wang Y Y, Wang K, Jin L K, et al. Kinetic modeling and process optimization of avilamycin production. Journal of Chemical Engineering of Chinese Universities, 2019,33(5):1156-1163.
[61] Méndez C, Salas J A. The role of ABC transporters in antibiotic-producing organisms: drug secretion and resistance mechanisms. Research in Microbiology, 2001,152(3-4):341-350.
[62] Treede I, Jakobsen L, Kirpekar F, et al. The avilamycin resistance determinants AviRa and AviRb methylate 23S rRNA at the guanosine 2 535 base and the uridine 2 479 ribose. Molecular Microbiology, 2003,49(2):309-318.
pmid: 12828631
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