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《中国工程科学》 >> 2021年 第23卷 第5期 doi: 10.15302/J-SSCAE-2021.05.009

微生物药物产业现状与发展趋势

上海交通大学微生物代谢国家重点实验室,上海 200240

资助项目 :中国工程院咨询项目“中国微生物安全与健康产业发展战略研究”(2020-ZD-05) 收稿日期: 2021-07-09 修回日期: 2021-08-30 发布日期: 2021-10-20

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摘要

微生物来源的天然产物药物具有结构多样、活性优良等优点,临床应用潜力巨大。本研究系统分析了我国微生物药物产业发展现状,梳理了微生物种质资源利用、优良菌种筛选和发酵工艺优化、菌株工程化改造、新型微生物药物创制等技术趋势,助力我国破解产业瓶颈、加速产业升级。我国现代微生物药物产业已经具备了坚实的资源和技术基础,但与国际领先水平有一定的差距。本研究针对产业面临的机遇与挑战,从建立统筹创新的微生物医药大科学装置、加强微生物药物基础研究和技术自主研发、构建战略性人才引育系统、形成体系化产业激励政策等四个方面提出了发展建议。

参考文献

[ 1 ] Abdel-Razek A S, El-Naggar M E, Allam A, et al. Microbial natural products in drug discovery [J]. Processes, 2020, 8(4): 1–19. 链接1

[ 2 ] Newman D J, Cragg G M. Natural products as sources of new drugs over the nearly four decades from 01/1981 to 09/2019 [J]. Journal of Natural Products, 2020, 83(3): 770–803. 链接1

[ 3 ] Demain A L, Sanchez S. Microbial drug discovery: 80 years of progress [J]. Journal of Antibiotics, 2009, 62(1): 5–16. 链接1

[ 4 ] 生物医药产业“十二五”开局 [J]. 中国经济和信息化, 2011 (9): 74–75. The status of biopharmaceutical industry at the “12th Five-Year Plan” opening [J]. China Economy & Informatization, 2011 (9): 74–75.
The status of biopharmaceutical industry at the “12th Five-Year Plan” opening [J]. China Economy & Informatization, 2011 (9): 74–75. Chinese. 链接1

[ 5 ] 李炎炎, 高山行. 中国生物医药产业发展现状分析——基于 1995—2015年统计数据 [J]. 中国科技论坛, 2016 (12): 42–47, 97. Li Y Y, Gao S X. Biopharmaceutical industry’s developing situation based on statistical data from 1995 to 2015 [J]. Forum on Science and Technology in China, 2016 (12): 42–47, 97.
Li Y Y, Gao S X. Biopharmaceutical industry’s developing situation based on statistical data from 1995 to 2015 [J]. Forum on Science and Technology in China, 2016 (12): 42–47, 97. Chinese. 链接1

[ 6 ] Kudo F, Eguchi T. Aminoglycoside antibiotics: New insights into the biosynthetic machinery of old drugs [J]. Chemical Record, 2016, 16(1): 4–18. 链接1

[ 7 ] 郝天怡, 赫卫清. 大环内酯类抗生素代谢工程的研究进展 [J]. 生 物工程学报, 2021, 37(5): 1737–1747. Hao T Y, Hao W Q. Advances in metabolic engineering of macrolide antibiotics [J]. Chinese Journal of Biotechnology, 2021, 37(5): 1737–1747.
Hao T Y, Hao W Q. Advances in metabolic engineering of macrolide antibiotics [J]. Chinese Journal of Biotechnology, 2021, 37(5): 1737–1747. Chinese. 链接1

[ 8 ] 李振, 殷瑜, 陈代杰. 四环素类抗生素的复苏 [J/OL]. 中国抗生素 杂志: 1–7. [2021-09-06]. https://doi.org/10.13461/j.cnki.cja.007168. Li Z, Yin Y, Chen D J. The tetracyclines resuscitation [J/OL]. Chinese Journal of Antibiotics: 1–7. [2021-09-06]. https://doi. org/10.13461/j.cnki.cja.007168.
Li Z, Yin Y, Chen D J. The tetracyclines resuscitation [J/OL]. Chinese Journal of Antibiotics: 1–7. [2021-09-06]. https://doi. org/10.13461/j.cnki.cja.007168. Chinese. 链接1

[ 9 ] 孟思童. 林可霉素生物合成的高产及硝酸盐效应机制解析 [D]. 上海: 上海交通大学(博士学位论文), 2017. Meng S T. Overproduction mechanism and nitrate stimulating effect on Lincomycin biosynthesis [D]. Shanghai: Journal of Shanghai Jiaotong University (Doctoral dissertation), 2017.
Meng S T. Overproduction mechanism and nitrate stimulating effect on Lincomycin biosynthesis [D]. Shanghai: Journal of Shanghai Jiaotong University (Doctoral dissertation), 2017. Chinese. 链接1

[10] 谢婷, 刘守强, 张宏周, 等. 林可霉素生产中三级种子罐的发酵 工艺优化 [J]. 微生物学通报, 2020, 47(12): 4359–4365. Xie T, Liu S Q, Zhang H Z, et al. Optimization of fermentation process of the third-stage seed fermenter in lincomycin production [J]. Microbiology China, 2020, 47(12): 4359–4365.
Xie T, Liu S Q, Zhang H Z, et al. Optimization of fermentation process of the third-stage seed fermenter in lincomycin production [J]. Microbiology China, 2020, 47(12): 4359–4365. Chinese. 链接1

[11] Gordaliza M. Natural products as leads to anticancer drugs [J]. Clinical & Translational Oncology, 2007, 9(12): 767–776. 链接1

[12] 赵东方, 何荣景, 侯旭东, 等. 源于天然的酶抑制剂高效发现及 评价新技术:进展与展望 [J]. 上海中医药大学学报, 2021, 35(1): 1–11, 19. Zhao D F, He R J, Hou X D, et al. New technologies for efficient discovery and evaluation of natural enzyme inhibitors: Research progress and perspectives [J]. Academic Journal of Shanghai University of Traditional Chinese Medicine, 2021, 35(1): 1–11, 19.
Zhao D F, He R J, Hou X D, et al. New technologies for efficient discovery and evaluation of natural enzyme inhibitors: Research progress and perspectives [J]. Academic Journal of Shanghai University of Traditional Chinese Medicine, 2021, 35(1): 1–11, 19. Chinese. 链接1

[13] 唐章勇, 唐灿. 酶抑制剂筛选的研究进展 [J]. 上海医药, 2007 (3): 117–119. Tang Z Y, Tang C. Research progress in screening enzyme inhibitors [J]. Shanghai Medical & Pharmaceutical Journal, 2007 (3): 117–119.
Tang Z Y, Tang C. Research progress in screening enzyme inhibitors [J]. Shanghai Medical & Pharmaceutical Journal, 2007 (3): 117–119. Chinese. 链接1

[14] Kisukuri C M, Andrade L H. Production of chiral compounds using immobilized cells as a source of biocatalysts [J]. Organic & Biomolecular Chemistry, 2015, 13(40): 10086–10107. 链接1

[15] Wang G, Haringa C, Noorman H, et al. Developing a computational framework to advance bioprocess scale-up [J]. Trends Biotechnol, 2020, 38(8): 846–856. 链接1

[16] Elibol M. Product shifting by controlling medium pH in immobilised Streptomyces coelicolor A3(2) culture [J]. Process Biochemistry, 2002, 37(12): 1381–1386. 链接1

[17] Chakravarty I, Kundu S. Improved production of Daptomycin in an airlift bioreactor by morphologically modified and immobilized cells of Streptomyces roseosporus [J]. AMB Express, 2016, 6(1): 101. 链接1

[18] Tan Z L, Zheng X, Wu Y, et al. In vivo continuous evolution of metabolic pathways for chemical production [J]. Microb Cell Fact, 2019, 18(1): 82. 链接1

[19] Douma R D, Verheijen P J T, de Laat W T A M, et al. Dynamic gene expression regulation model for growth and penicillin production in penicillium chrysogenum [J]. Biotechnology and Bioengineering, 2010, 106(4): 608–618. 链接1

[20] Veiter L, Kager J, Herwig C. Optimal process design space to ensure maximum viability and productivity in Penicillium chrysogenum pellets during fed-batch cultivations through morphological and physiological control [J]. Microb Cell Fact, 2020, 19(1): 33. 链接1

[21] Schadel F, Franco-Lara E. Rapid sampling devices for metabolic engineering applications [J]. Applied Microbiology Biotechnology, 2009, 83(2): 199–208. 链接1

[22] Weber T, Charusanti P, Musiol-Kroll E M, et al. Metabolic engineering of antibiotic factories: New tools for antibiotic production in actinomycetes [J]. Trends in Biotechnology, 2015, 33(1): 15–26. 链接1

[23] 欧竑宇. 链霉菌基因组岛和次生代谢物合成相关的生物信息学 工具及数据库 [J]. 微生物学通报, 2013, 40(10): 1909–1919. Ou H Y. Bioinformatics tools and databases focused on genomic islands and secondary metabolite biosynthesis of Streptomyces [J]. Microbiology China, 2013, 40(10): 1909–1919.
Ou H Y. Bioinformatics tools and databases focused on genomic islands and secondary metabolite biosynthesis of Streptomyces [J]. Microbiology China, 2013, 40(10): 1909–1919. Chinese. 链接1

[24] Doroghazi J R, Albright J C, Goering A W, et al. A roadmap for natural product discovery based on large-scale genomics and metabolomics [J]. Nature Chemical Biology, 2014, 10(11): 963– 968. 链接1

[25] Medema M H, Blin K, Cimermancic P, et al. antiSMASH: Rapid identification, annotation and analysis of secondary metabolite biosynthesis gene clusters in bacterial and fungal genome sequences [J]. Nucleic Acids Research, 2011, 39: W339–346. 链接1

[26] Boddy C N. Bioinformatics tools for genome mining of polyketide and non-ribosomal peptides [J]. Journal of Industrial Microbiology & Biotechnology, 2014, 41(2): 443–450. 链接1

[27] Lyu J M, Hu D, Gao H, et al. Biosynthesis of helvolic acid and identification of an unusual C-4-demethylation process distinct from sterol biosynthesis [J]. Nature Communications, 2017, 8(1): 1644. 链接1

[28] Malico A A, Nichols L, Williams G J. Synthetic biology enabling access to designer polyketides [J]. Current Opinion in Chemical Biology, 2020 (58): 45–53. 链接1

[29] Ajikumar P K, Xiao W H, Tyo K E, et al. Isoprenoid pathway optimization for Taxol precursor overproduction in Escherichia coli [J]. Science, 2010, 330(6000): 70–74. 链接1

[30] Zhou Y J, Gao W, Rong Q, et al. Modular pathway engineering of diterpenoid synthases and the mevalonic acid pathway for miltiradiene production [J]. Journal of the American Chemical Society, 2012, 134(6): 3234–3241. 链接1

[31] Paddon C J, Westfall P J, Pitera D J, et al. High-level semisynthetic production of the potent antimalarial artemisinin [J]. Nature, 2013, 496(7446): 528. 链接1

[32] Ozber N, Watkins J L, Facchini P J. Back to the plant: Overcoming roadblocks to the microbial production of pharmaceutically important plant natural products [J]. Journal of Industrial Microbiology & Biotechnology, 2020, 47(9–10): 815–828. 链接1

[33] Menchaca R, Martinez V, Rodriguez A, et al. Synthesis of natural ecteinascidins (ET-729, ET-745, ET-759B, ET-736, ET-637, ET594) from cyanosafracin B [J]. Journal of Organic Chemistry, 2003, 68(23): 8859–8866. 链接1

[34] 卢俊南, 褚鑫, 潘燕平, 等. 基因编辑技术:进展与挑战 [J]. 中国 科学院院刊, 2018, 33(11): 1184–1192. Lu J N, Chu X, Pan Y P, et al. Advances and Challenges in Gene Editing Technologies [J]. Bulletin of Chinese Academy of Sciences, 2018, 33(11): 1184–1192.
Lu J N, Chu X, Pan Y P, et al. Advances and Challenges in Gene Editing Technologies [J]. Bulletin of Chinese Academy of Sciences, 2018, 33(11): 1184–1192. Chinese. 链接1

[35] Xu M, Zhang F, Cheng Z, et al. Functional genome mining reveals a class v lanthipeptide containing a d-Amino acid introduced by an F420 H2 -dependent reductase [J]. Angewandte ChemieInternational Edition, 2020, 59(41): 18029–18035. 链接1

[36] 胡黔楠, 吴玲, 涂伟忠, 等. 微生物药物生物合成知识库研究进 展 [J]. 生物产业技术, 2015 (6): 59–62. Hu Q N, Wu L, Tu W Z, et al. The trends in microbial drug biosynthetic databases [J]. Biotechnology & Business, 2015 (6): 59–62.
Hu Q N, Wu L, Tu W Z, et al. The trends in microbial drug biosynthetic databases [J]. Biotechnology & Business, 2015 (6): 59–62. Chinese. 链接1

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