国家优秀青年基金获得者 马俊英研究员(2020)
副标题:
马俊英博士 研究员
(海洋微生物天然产物的发现及其生物合成学科组 majunying@scsio.ac.cn)
研究领域
海洋放线菌源环肽抗感染、抗肿瘤环肽的发现、生物合成和作用机制研究。包括:
1)活性环肽化合物生物合成基因簇的克隆、鉴定及异源表达;
2)活性环肽分子的生物工程改造及组合生物合成;
3)海洋微生物活性次级代谢产物的基因组挖掘;
4)海洋药物先导的作用机制研究。
代表性工作简介
代表性学术成绩:I)发现了抗感染、抗肿瘤海洋放线菌源环肽50余个,解析了5个抗感染、抗肿瘤环肽的生物合成途径并实现了其异源表达,构建了96个基因敲除双交换突变株,其中包括9株高产工程菌株;II)阐明了4个环肽分子及其10个非天然氨基酸机构单元的生物合成机制,发现了8个具有应用潜力了生物合成酶;III)阐明了抗结核候选药物怡莱霉素E和抗三阴乳腺癌药物先导怡莱霉素C的作用机制,完成了抗结核怡莱霉素E的成药性评价。主持国家自然科学基金委优秀青年科学基金项目、面上项目、青年科学基金项目、国家重点研发计划子课题、中科院青年创新促进会专项基金、广东省自然科学基金面上项目、广东省特支计划百千万工程青年拔尖人才项目和中科院南海新星等项目10余项。在Nat. Commun.、Angew. Chem. Int. Ed.、J. Hematol. Oncol.、Org. Lett.等杂志发表SCI论文40余篇,其中第一作者、通讯或共同通讯作者论文15篇,SCI他引800余次,获得授权专利8件,参编3部专著章节。
2020年获得国家自然科学基金委优秀青年科学基金项目资助,2019年入选“中国药学会海洋药物专业委员会”青年委员;2016年入选“广东省特支计划”百千万工程青年拔尖人才,2014年获得广东省科学技术二等奖(排名第9),2013年入选“广州市珠江科技新星”,2012年入选“中科院青年创新促进会”会员;2010年获得“广东省优秀博士学位论文”,2009年获得“华南农业大学优秀博士学位论文”。
工作经历
2009.07-2011.11:中国科学院南海海洋研究所,助理研究员
2011.12-2013.12:中国科学院南海海洋研究所,副研究员
2014.01-2017.11:中国科学院南海海洋研究所,副研究员,硕士生导师
2016.04-2017.04:加州大学伯克利分校,访问学者
2017.12-至今:中国科学院南海海洋研究所,研究员,硕士生导师
2020.8-至今: 中国科学院南海海洋研究所,研究员,博士生导师
教育背景
2000.09-2004.07:河南农业大学,动物科学, 学士学位
2004.09-2009.07:华南农业大学,兽医药理学,博士学位(硕博连读)
获奖及荣誉
1. 入选“广东省百千万青年拔尖人才”(2016)
2. 获得广东省科学技术二等奖(排名第9)(2014)
3. 入选“广州市珠江科技新星”(2013)
4. 入选“中科院青年创新促进会”会员(2012)
5. 获得“广东省优秀博士学位论文”(2010)
6. 获得“华南农业大学优秀博士毕业论文”(2009)
学术兼职
1. 白求恩青年科学家委员会委员(2018-至今)
2. 中国药学会海洋药物专业委员会青年委员会委员(2019-2024)
代表性学术成果
论文发表
1. Xie, Q.;# Yang, Z.;# Huang, X.; Zhang, Z.; Li, J.; Ju, J.;* Zhang, H.;* Ma, J.*Ilamycin C induces apoptosis and inhibits migration and invasion in triple-negative breast cancer by suppressing IL-6/STAT3 pathway. J. Hemat. Onco. 2019, doi: 10.1186/s13045-019-0744-3. (IF2019=11.05)
2. Ma, J.;* Huang, H.; Xie, Y.; Liu, Z.; Zhao, J.; Jia, Y.; Zhang, C.; Zhang, Y.; Zhang, H.; Zhang, T.; Ju, J.* Biosynthesis of ilamycins featuring unusual building blocks and engineered production of enhanced anti-tuberculosis agents. Nat. Commun. 2017, 8(1), 391(doi: 10.1038/s41467-017-00419-5). (IF2017=12.353)
3. Ma, J.; Wang, Z.; Huang, H.; Zuo, D.; Luo, M.; Wang, B.; Sun, A.; Cheng, Y.; Zhang, C.; Ju, J.* Biosynthesis of himastatin: Assembly line and characterization of three cytochrome P450 enzymes involved in the post-tailoring oxidative steps. Angew. Chem. Int. Ed. 2011, 50, 7797-7802. (IF2011=13.455) (highlighted by Faculty of 1000).
4. Sun, C.; Yang, Z.; Zhang, C.; Liu, Z.; He, J.; Liu, Q.; Zhang, T.; Ju, J.;* Ma, J.* Genome mining of Streptomyces atratus SCSIO ZH16: discovery of atratumycin and identification of its biosynthetic gene cluster. Org. Lett. 2019, 21, 1453-1457.
5. Yang, Z.;# Sun, C.;# Liu, Z.; Liu, Q.; Zhang, T.; Ju, J.;* Ma, J.* Production of antitubercular depsipeptides via biosynthetic engineering of cinnamoyl units. J. Nat. Prod. 2020, 83, 1666-1673
6. Sun, C.;# Liu, Z.;# Zhu, X.; Fan, Z.; Huang, X.; Wu, Q.; Zheng, X.; Qin, X.; Zhang, T.; Zhang, H.; Ju, J.;* Ma, J.* Antitubercular ilamycins from marine-derived Streptomyces atratus SCSIO ZH16 ΔilaR. J. Nat. Prod. 2020, 83, 1646-1657.
7. He, J.; Wei, X.; Yang, Z.; Li, Y.; Ju, J.; Ma, J.* Characterization of regulatory and transporter genes in the biosynthesis of anti-tuberculosis ilamycins and production in a heterologous host. Mar. Drugs. 2020, 18(4). pii: E216.
8. Yang, Z.; Wei, X.; He, J.; Sun, C.; Ju, J.;* Ma, J.* Characterization of the noncanonical regulatory and transporter genes in Atratumycin biosynthesis and production in a heterologous host. Mar. Drug 2019, 17(10), E560.
9. Xie, Y.; Li, Q.; Qin, X.; Ju, J. ;* Ma, J.* Enhancement of himastatin bioproduction via inactivation of atypical repressors in Streptomyces hygroscopicus. Metab. Eng. Commun. 2019, 8, e00084.
10. Huang, X.; Yang, Z.; Xie, Q.; Zhang, Z.; Zhang, H.; Ma, J.* Natural products for treating colorectal cancer: A mechanistic review. Biomed. Pharmacother. 2019, doi.org/10.1016/j.biopha.2019.109142.
11. Yang, Z.; He, J.; Wei, X.; Ju, J.; Ma, J.* Exploration and genome mining of natural products from marine Streptomyces. Appl. Microbiol. Biotechnol. 2020, 104, 67-76.
12. Li, Y.; Zhang, C.; Liu, C.; Ju, J.;* Ma, J.* Genome sequencing of Streptomyces atratus SCSIOZH16 and activation production of Nocardamine via metabolic engineering. Front Microbiol. 2018, 9, 1269. doi: 10.3389/fmicb.2018.01269.
13. Ma, J.; Zeng, Z.; Chen, Z.; Xu, X.; Wang, X.; Deng, Y.; Lü, D.; Huang, L.; Zhang, Y.; Liu, J.;*Wang, M.* High prevalence of plasmid-mediated quinolone resistance determinants qnr, aac(6')-Ib-cr, and qepA among ceftiofur-resistant Enterobacteriaceae isolates from companion and food-producing animals. Antimicrob. Agents Chemother. 2009, 53, 519-524.
14. Ma, J.; Zuo, D.; Song, Y.; Huang, H.; Yao, Y.; Li, W.; Zhang, C.; Ju, J.* Characterization of a single gene cluster that is responsible for methylpendolmycin and pendolmycin biosynthesis in the deep sea bacterium Marinactinospora thermotolerans. ChemBioChem 2012, 13, 547-552.
15. Ma, J.; # Liu, J.; #* Lv, L.; Zong, Z.; Sun, Y.; Zheng, H.; Chen, Z.; Zeng, Z. * Characterization of extended-spectrum β-lactamase genes found among Escherichia coli isolates from duck and environmental samples obtained on a duck farm. Appl. Environ. Microbiol. 2012 , 78, 3668-3673.
16. Mo, X.; Ma, J.; Huang, H.; Wang, B.; Song, Y.; Zhang, S.; Zhang, C.; Ju, J.* ?11,12-double bond formation in tirandamycin biosynthesis is atypically catalyzed by TrdE, a glycoside hydrolase family enzyme. J. Am. Chem. Soc. 2012, 134, 2844-2847.
17. Xie, Y.; Ma, J.; Qin, X.; Li, Q.; Ju, J.* Identification and utilization of two important transporters: SgvT1 and SgvT2, for griseoviridin and viridogrisein biosynthesis in Streptomyces griseoviridis. Microb. Cell Fact. 2017, 16(1): 177.
18. Shao, M.; Ma, J.; Li, Q.; Ju, J.* Identification of the anti-infective aborycin biosynthetic gene cluster from deepsea-derived Streptomyces sp. SCSIO ZS0098 enables production in a heterologous host. Mar. Drugs 2019, 17, 127( doi:10.3390/md17020127).
19. Mo, X.; Huang, H.; Ma, J.; Wang, Z.; Wang, B.; Zhang, S.; Zhang, C.; Ju J.* Characterization of TrdL as a 10-hydroxy dehydrogenase and generation of new analogues from a tirandamycin biosynthetic pathway. Org. Lett. 2011, 13, 2212-2215.
20. Zhu, Q.; Li, J.; Ma, J.; Luo, M.; Wang, B.; Huang, H.; Tian, X.; Li, W.; Zhang, S.; Zhang, C.; Ju, J.* Discovery and engineered overproduction of antimicrobial nucleoside antibiotic A201A from deep sea marine actinomycete Marinactinospora thermotolerans SCSIO 00652. Antimicrob. Agents Chemother. 2012, 56, 110-114.
21. Zhang, C.; Yang, Z.; Qin, X.; Ma, J.; Sun, C.; Huang, H.; Li, Q.; Ju, J. * Genome mining for mycemycin: discovery and elucidation of related methylation and chlorination biosynthetic chemistries. Org. Lett. 2018, 20, doi: 10.1021/acs.orglett.8b03373.
22. Xie, Y.; Li, Q.; Song, Y.; Ma, J.; Ju, J.* Involvement of SgvP in carbon–sulfur bond formation during griseoviridin biosynthesis. ChemBioChem 2014, 15, 1183-1189 (commented by Faculty of 1000).
23. Mo, X.; Wang, Z.; Wang, B.; Ma, J.; Huang, H.; Tian, X.; Zhang, S.; Zhang, C.; Ju, J.* Cloning and characterization of the biosynthetic gene cluster of the bacterial RNA polymerase inhibitor tirandamycin from marine-derived Streptomyces sp. SCSIO1666. Biochem. Biophy. Res. Commun., 2011, 406, 341-347.
24. Gui, C.;# Li, Q.;# Mo, X.;# Qin, X.; Ma, J; Ju, J.* Discovery of a new family of Dieckmann cyclases essential to tetramic acid and pyridone-based natural products biosynthesis. Org. Lett. 2015, 17, 628-631.
25. Liu, M.; Jia, Y.; Xie, Y.; Zhang, C.; Ma, J.; Sun, C.; Ju, J.* Identification of the actinomycin D biosynthetic pathway from marine-derived Streptomyces costaricanus SCSIO ZS0073. Mar. Drugs 2019, 17, 240.
26. Qin, X.; Xie, Y.; Huang, H.; Chen, Q.; Ma, J.; Li, Q.; Ju, J.* Enzymatic synthesis of GDP-?-L-fucofuranose by MtdL and Hyg20. Org. Lett. 2018, 20, 1015-1018.
27. Chen, Q.; Ji, C.; Song, Y.; Huang, H.; Ma, J.; Tian, Xi.; Ju, J.* Discovery of McbB, a novel enzyme catalyzing the β-Carboline skeleton construction in the marinacarboline biosynthetic pathway. Angew. Chem. Int. Ed. 2013, 52, 9980-9984 (commented by Faculty of 1000).
28. Wang, B.; Song, Y.; Luo, M.; Chen, Q.; Ma, J.; Huang, H.; Ju, J.* Biosynthesis of 9-methylstreptimidone involves a new decarboxylative step for polyketide terminal diene formation. Org. Lett. 2013, 15, 1278-1281.
29. Xie, Y.; Wang, B.; Liu, J.; Zhou, J.; Ma, J.; Huang, H.; Ju, J. Identification of the Biosynthetic Gene Cluster and Regulatory Cascade for the Synergistic Antibacterial Antibiotics Griseoviridin and Viridogrisein in Streptomyces griseoviridis. ChemBiochem 2012, 13, 2745-2457.
30. Huang, H.; Yao, Y.; He, Z.; Yang, T.; Ma, J.; Tian, X.; Li, Y.; Huang, C.; Chen, X.; Li, W.; Zhang, S.; Zhang, C.; Ju, J.* Antimalarial ?-carboline and indolactam alkaloids from Marinactinospora thermotolerans, a deep sea isolate. J. Nat. Prod. 2011, 74, 2122-2127.
31. Chen, Z.; Huang, H; Chen, Y.; Wang, Z.; Ma, J.; Wang, B.; Zhang, W.; Zhang, C.; Ju, J.* New cytochalasins from the marine-derived fungus Xylaria sp. SCSIO 156. Helv. Chim. Acta. 2011, 94, 1671-1676.
32. Zhu, Q.; Chen, Q.; Song, Y.; Huang, H.; Li, J.; Ma, J.; Li, Q.; Ju, J.* Deciphering the sugar biosynthetic pathway and tailoring steps of nucleoside antibiotic A201A unveils a GDP-L-galactose mutase. Proc. Natl. Acad. Sci. USA. 2017, 114, 4948-4953.
33. Chen, Z.; Zheng, Z.; Huang, H.; Song, Y.; Zhang, X., Ma, J.; Wang, B.; Zhang, C.; Ju, J.* Penicacids A-C, three new mycophenolic acid derivatives and immunosuppressive activities from the marine-derived fungus Penicillium sp. SOF07. Bioorg. Med. Chem. Lett. 2012, 22, 3332-3325.
34. Gui, C.; Chen, J.; Xie, Q.; Mo, X.; Zhang, S.; Zhang, H.; Ma, J.; Li, Q.; Gu, Y-C.; Ju, J.* CytA, a reductase in the cytorhodin biosynthesis pathway, inactivates anthracycline drugs in Streptomyces. Commun. Biol., 2019, 2, 454 (https://doi.org/10.1038/s42003-019-0699-5).
35. Zhang, Y.; Huang, H.; Chen, Q.; Luo, M.; Sun, A.; Song, Y.; Ma, J.; Ju, J.* Identification of the grincamycin gene cluster unveils divergent roles for GcnQ in different hosts, tailoring the L-rhodinose moiety. Org. Lett. 2013, 15, 3254-3257.
36. Huang, H.; Yang, T.; Ren, X.; Liu, J.; Song, Y.; Sun, A.; Ma, J.; Zhang, Y.; Huang, C.; Zhang, C.; Ju, J.* Cytotoxic angucycline class glycosides from the deep sea actinomycete Streptomyces lusitanus SCSIO LR32. J. Nat. Prod. 2012, 75, 202-208.
37. Liu, J.; Wei, S.; Ma, J.; Zeng, Z.; Lü, D.; Yang, G.; Chen, Z. Detection and characterization of CTX-M and CMY-2 beta-lactamases among Escherichia coli isolates from farm animals in Guangdong Province of China. Int. J. Antimicrob. Agents 2007, 29, 576-581.
38. Sun, Y.; Zeng, Z.; Chen, S.; Ma, J.; He, L.; Liu, Y.; Deng, Y.; Lei, T.; Zhao, J.; Liu, J. High prevalence of bla(CTX-M) extended-spectrum β-lactamase genes in Escherichia coli isolates from pets and emergence of CTX-M-64 in China. Clin. Microbiol. Infect. 2010, 16, 1475-1481.
39. Chen, L.; Chen, Z.; Liu, J.; Zeng, Z.; Ma, J.; Jiang H. Emergence of RmtB methylase-producing Escherichia coli and Enterobacter cloacae isolates from pigs in China. J. Antimicrob. Chemother. 2007, 59, 880-885.
40. Deng, Y.; He, L.; Chen, S.; Zheng, H.; Zeng, Z.; Liu, Y.; Sun, Y.; Ma, J.; Chen, Z.; Liu, J. * F33:A-:B- and F2:A-:B- plasmids mediate dissemination of rmtB-blaCTX-M-9 group genes and rmtB-qepA in Enterobacteriaceae isolates from pets in China. Antimicrob. Agents Chemother. 2011, 55, 4926-4929.
授权专利
1. 环酯肽类抗生素黑莫他丁的高产菌株及其构建方法,鞠建华,马俊英,张云,李青连,黄洪波,宋永相,王博,谢运昌,ZL2014103727287
代表性学术成果
1. 优秀青年科学基金项目:天然药物化学(82022067),2021.01-2023.12,120万元,在研,主持。
2. 中科院南海海洋研究所“南海新星”项目含肉桂酸结构单元抗结核环肽化合物的基因组挖掘(NHXX2019SW0101),2019.10-2022.10,100万元,主持。
3. 国家自然科学基金面上项目:深海链霉菌 Streptomyces atratus SCSIO ZH16中新颖环肽化合物atramycin的代谢激活及其生物合成机制(31870046),2019.01-2022.12,59万元,在研,主持。
4. 国家重点研发计划课题三-子课题:微生物天然产物的智能创制与改良-新结构和新功能天然产物的合成体系的智能创建(2019YFA0901903),2019.01-2023.12,80万元,在研,主持。
5. 国家自然科学基金应急项目:深海放线菌源抗结核抗生素怡莱霉素E的作用机制及体内药效学研究(81741166),2018.01-2018.12,20万元, 结题,主持。
6. 广东省特支计划:百千万工程青年拔尖人才“基于CRISP-cas9技术的Streptomyces atratus SCSIO ZH16的基因组挖掘(201528018),2016.01-2018.12. 10万元,结题,主持。
7. 国家自然科学基金面上项目:抗菌环肽类抗生素ilamycin的生物合成研究(20872152),2013.01-2016.12,76万元,结题,主持。
8. 国家自然科学青年基金项目:抗肿瘤抗生素海沟霉素A和B的生物合成及其功能基因研究 (31000051),2011.01-2013.12,19万元,结题,主持。
9. 中国科学院创新促进会会员专项基金:2013.01-2016.12,40万元,结题,主持。
10. 广州市“珠江科技新星”人才专项基金:抗肿瘤抗生素marthiapeptide A 的生物合成机制及其工程改造(2014J2200089),2014.04-2017.03,30万元,结题,主持。
11. 中国科学院青年人才前沿领域项目:海洋放线菌来源的β-卡啉生物碱 Marinocarboline A-F的生物合成机制研究 (SQ201015),2011.10-2013.10,8万元,结题,主持。
12. 国家科技合作与交流专项:中美合作开发新型?-内酰胺酶抑制剂(2011DFA32540), 2012.01-2014.12,44.93万元,结题,主持。
研究生招生及培养情况
硕士研究生:杨志杰(2017级),何建桥(2018级),韦歆(2019级)
培养5名硕士研究生(2名已毕业,3名硕士在读),其中2名获得国家研究生奖学金。
招收硕士/博士研究生。招生专业一:海洋生物学(方向1:海洋微生物代谢工程、海洋生物技术);招生专业二:生物工程。每年9月份接受985、211工程等院校生物技术、生物工程、化学和药学专业推荐免试直博生和推荐免试硕士生各1名,接受联合培养硕士/博士研究生。