1 抗菌肽
1.1 抗菌肽作用机制
本团队首次系统提出抗菌肽“源于胞内相近相容、高敏预警早期防御”高效入胞和“强穿膜、多靶点”低耐药机制和铁三角理论。正在进行抗菌肽作用病原菌细胞壁、细胞膜以及胞内大分子等靶标的挖掘和鉴定，并借助编辑/解码器等高通量智能筛选和解析低耐药强抗菌关键结构间的构效量效关系。
1.2 抗菌肽创制关键技术
在国内外率先建成抗菌肽现代生物制造体系，20/30m3规模先导产品生泰素发酵规模，蛋白表达量达3.14g/L，蛋白纯度>92%，日产能2kg/d，成本<70元/g。连续稳定运行七批次，制备纯品49kg，具抗菌肽生物工程路径走通并落地成功的重要技术标志和里程碑意义。目前正在（1）建立抗菌肽高产节能型制备体系，进行抗G+菌肽节能高产制备系统升级及抗G-菌肽高产制备系统的拓展；（2）抗菌肽修饰工程化研究（包括环化、纳米自组装、包被及适配体偶联等）；（3）抗菌肽成药性关键检测技术研究；（4）抗菌肽制剂开发研究。
1.3 抗菌肽应用
拓展抗菌肽对靶动物应用细分：防治奶牛乳房炎、母畜子宫内膜炎、家禽细菌性腹泻、水产细菌病、宠物等皮肤感染等。开展抗菌肽对上述适应症的靶动物药效、田间药效、安全性、药代动力学、残留消除等临床研究。
针对饼粕原料致敏蛋白含量高、发酵菌种多元、工艺粗放和质量不稳等瓶颈，筛评建立专用菌种库，创建致敏蛋白等抗营养因子分子检测方法、发酵工艺流程。制/修定首个发酵饲料原料标准《饲料原料发酵豆粕》，填补界定豆粕发酵程度和产品品质的空白，规范发酵工艺，对保障产品质量、满足细分需求、破解瓶颈问题具重要作用。
2 发酵饲料原料
针对饼粕原料致敏蛋白含量高、发酵菌种多元、工艺粗放和质量不稳等瓶颈，筛评建立专用菌种库，创建致敏蛋白等抗营养因子分子检测方法、发酵工艺流程。制/修定首个发酵饲料原料标准《饲料原料 发酵豆粕》，填补界定豆粕发酵程度和产品品质的空白，规范发酵工艺，对保障产品质量、满足细分需求、破解瓶颈问题具重要作用。
科技奖励
1. 2018-2019年神农中华农业科技奖一等奖，新型饲用抗生素替代品创制及应用，2019-KJ027-1-D01.
2. 2017年度北京市科学技术奖一等奖，新型饲用抗生素替代品创制与应用，2017-农-1-001.
3. 2005年北京科学技术二等奖，动物用微生态制剂研制与开发，2005农-2-002-01.
4. 2004年北京科学技术二等奖，高产菊粉酶酵母与菊粉高果糖浆制备技术，2004农- 2-003-01.
5. 2001年度国家科技进步二等奖，基因工程酵母生产饲料用植酸酶，J-203-2-05-R03.
6. 第十八届中国高新技术成果交易会优秀产品奖：专抗革兰氏阳性菌的新型抗菌肽制剂
新产品
1. 食品级外切菊粉酶INU2000, 国家级重点新产品编号：2002ED326016, 2002
2. 高纯度低聚合度低聚果糖FOS80, 国家级重点新产品编号：2005ED125005, 2005
制定标准
1. 制定农业行业标准《饲料添加剂 产朊假丝酵母》 NY/T1969-2010.
2. 制定农业行业标准《饲料原料 发酵豆粕》NY/T2218-2012.
3. 修订农业行业标准《饲料原料 发酵豆粕》NY/T2218-2022.
发表论文与专著
1. Zheng XL, Yang N, Mao RY, Hao Y, Teng D, Wang JH. Pharmacokinetics and pharmacodynamics of fungal defensin NZX against Staphylococcus aureus-induced mouse peritonitis model. Front Microbiol. 2022, 13:865774.
2. Wu YK, Yang N, Mao RY, Hao Y, Teng D, Wang JH. In vitro pharmacodynamics and bactericidal mechanism of fungal defensin-derived peptides NZX and P2 against Streptococcus agalactiae. Microorganisms. 2022, 10(5):881.
3. Zheng XL, Teng D, Mao RY, Hao Y, Yang N, Hu FM, Wang JH. A study on fungal defensin against multidrug-resistant Clostridium perfringens and its treatment on infected poultry. Appl Microbiol Biotechnol. 2021 , 105(19):7265-7282.
4. Ma XX, Yang N, Mao RY, Hao Y, Yan X, Teng D, Wang JH. The pharmacodynamics study of insect defensin DLP4 against toxigenic Staphylococcus hyicus ACCC 61734 in vitro and vivo. Front Cell Infect Microbiol. 2021, 11:638598.
5. Liu H, Yang N, Teng D, Mao RY, Hao Y, Ma XX, Wang XM, Wang JH. Fatty acid modified-antimicrobial peptide analogues with potent antimicrobial activity and topical therapeutic efficacy against Staphylococcus hyicus. Appl Microbiol Biotechnol. 2021,105(14-15):5845-5859.
6. Han HH, Teng D, Mao RY, Hao Y, Yang N, Wang ZL, Li T, Wang XM, Wang JH. Marine peptide-N6NH2 and its derivative-GUON6NH2 have potent antimicrobial activity against intracellular Edwardsiella tarda in vitro and in vivo. Front Microbiol. 2021.12:637427.
7. Pen GH, Yang N, Teng D, Mao RY, Hao Y, Wang JH. A review on the use of antimicrobial peptides to combat porcine viruses. Antibiotics. 2020, 9(11):801.
8. Wang ZL, Liu X, Teng D, Mao RY, Hao Y, Yang N, Wang X, Li ZZ, Wang XM, Wang JH. Development of chimeric peptides to facilitate the neutralisation of lipopolysaccharides during bactericidal targeting of multidrug-resistant Escherichia coli. Commun Biol. 2020, 3(1):41.
9. Li T, Teng D, Mao RY, Hao Y, Wang XM, Wang JH. Recent progress in preparation and agricultural application of microcapsules. J Biomed Mater Res A. 2019,107(10):2371-2385.
10. Li ZZ, Wang X, Teng D, Mao RY, Hao Y, Yang N, Chen HX, Wang XM, Wang JH. Improved antibacterial activity of a marine peptide-N2 against intracellular Salmonella typhimurium by conjugating with cell-penetrating peptides-bLFcin6/Tat11. Eur J Med Chem. 2018, 10;145:263-272.
11. Li ZZ, Teng D, Mao RY, Wang X, Hao Y, Wang XM, Wang JH. Improved antibacterial activity of the marine peptide N6 against intracellular Salmonella typhimurium by conjugating with the cell-penetrating peptide Tat11 via a cleavable linker. J Med Chem. 2018, 61(17):7991-8000.
12. Yang N, Teng D, Mao RY, Hao Y, Wang X, Wang ZL, Wang XM, Wang JH. A recombinant fungal defensin-like peptide-P2 combats multidrug-resistant Staphylococcus aureus and biofilms. Appl Microbiol Biotechnol. 2019, 103(13):5193-5213.
13. Zhao F, Yang N, Wang XM, Mao RY, Hao Y, Li ZZ, Wang X, Teng D, Fan H, Wang JH. In vitro/vivo mechanism of action of MP1102 with low/nonresistance against Streptococcus suis type 2 strain CVCC 3928. Front Cell Infect Microbiol. 2019, 9:48.
14. Wang X, Wang XM, Teng D, Mao RY, Hao Y, Yang N, Li ZZ, Wang JH. Increased intracellular activity of MP1102 and NZ2114 against Staphylococcus aureus in vitro and in vivo. Sci Rep. 2018, 8(1):4204.
15. Wang ZL, Wang XM, Wang JH. Recent advances in antibacterial and antiendotoxic peptides or proteins from marine resources. Mar Drugs. 2018 16(2):57.
16. Hao Y, Yang N, Wang X, Teng D, Mao RY, Wang XM, Li ZZ, Wang JH. Killing of Staphylococcus aureus and Salmonella enteritidis and neutralization of lipopolysaccharide by 17-residue bovine lactoferricins: improved activity of Trp/Ala-containing molecules. Sci Rep. 2017, 7:44278.
17. Wang XM, Teng D, Mao RY, Yang N, Hao Y, Wang JH. Combined systems approaches reveal a multistage mode of action of a marine antimicrobial peptide against pathogenic Escherichia coli and its protective effect against bacterial peritonitis and endotoxemia. Antimicrob Agents Ch, 2016, 61(1):e01056-16.
18. Yang N, Wang XM, Teng D, Mao RY, Hao Y, Zong LF, Feng XJ, Wang JH. Modification and characterization of a new recombinant marine antimicrobial peptide N2. Process Biochem. 2016, 51:734-739.
19. Zong LF, Teng D, Wang XM, Mao RY, Yang N, Hao Y, Wang JH. Mechanism of action of a novel recombinant peptide, MP1102, against Clostridium perfringens type C. Appl Microbiol Biotechnol. 2016, 100:5045-5057.
20. Mao RY, Teng D, Wang XM, Zhang Y, Jiao J, Cao XT, Wang JH. Optimization of expression conditions for a novel NZ2114-derived antimicrobial peptide-MP1102 under the control of the GAP promoter in Pichia pastoris X-33. BMC Microbiology, 2015, 15: 57.
21. Teng D, Wang XM, Xi D, Mao RY, Zhang Y, Guan QF, Zhang J, Wang JH. A dual mechanism involved in membrane and nucleic acid disruption of AvBD103b, a new avian defensin from the king penguin, against Salmonella enteritidis CVCC3377. Appl Microbiol Biotechnol. 2014, 98(19): 8313-8325.
22. Zhang Y, Teng D, Mao RY, Wang XM, Xi D, Hu XY, Wang JH. High expression of a plectasin derived peptide-NZ2114 in Pichia pastoris and its pharmacodynamics, postantibiotic and synergy against Staphylococcus aureus. Appl Microbiol Biotechnol. 2014, 98(2): 681-694.
23. Zhang J, Yang YL, Teng D, Tian ZG, Wang SR, Wang JH. Expression of plectasin in Pichia pastoris and its characterization as a new antimicrobial peptide against Staphyloccocus and Streptococcus. Protein Expres Purif. 2011, 78(2): 189-196.
24. Tian ZG, Dong TT, Teng D, Yang YL, Wang JH. Design and characterization of novel hybrid peptides from LFB15(W4,10), HP(2-20), and cecropin A based on structure parameters by computer-aided method. Appl Microbiol Biotechnol. 2009, 82(6): 1097-1103.
25. Tian ZG, Dong TT, Yang YL, Teng D, Wang JH. Expression of antimicrobial peptide LH multimers in Escherichia coli C43(DE3). Appl Microbiol Biotechnol. 2009,83:143-149.
26. Yang YL, Tian ZG, Teng D, Zhang J, Wang JR, Wang JH. High-level production of a candidacidal peptide lactoferrampin in Escherichia coli by fusion expression. J Biotechnol. 2009,139(4): 326-331
27. 王建华,杨雅麟,滕达,张帆.生物饲料添加剂创新研究和产业发展的现状与对策.高技术通讯. 2004, 14(10): 94- 99.
28. 王建华主编,新型安全饲料添加剂研制与开发,科学出版社,2005(1版,40万字);2008(2版，70万字).
29. Wang JH, Dominique Legrand. Advances in lactoferrin R&D– proceedings of the ninth Int’l Conference on Lactoferrin Structure, Function and Application, BioMetals 2010,23(3):355-596, Springer, June 2010, Dordrecht, The Netherlands.
30. Wang JH, Octavio Luiz Franco, Cesar de la Fuente-Nunez. Front Microbiol. Research Topic. Antimicrobial peptides: molecular design, structure function relationship and biosynthesis optimization.
31.Kun Zhang;Da Teng;Ruoyu Mao;Na Yang;Ya Hao;Jianhua Wang. Thinking on the Construction of Antimicrobial Peptide Databases:Powerful Tools for the Molecular Design and Screening. International journal of molecular sciences.2023, 24(4): 24043134.
32.Ya Hao;Jianhua Wang;Cesar de la Fuente-Nunez;Octavio Luiz Franco. Editorial: Antimicrobial Peptides: Molecular Design, Structure-Function Relationship, and Biosynthesis Optimization. Frontiers in Microbiology.2023, 13: 888540.
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