小分子前体物对巴弗洛霉素A1生物合成的影响

doi:10.13560/j.cnki.biotech.bull.1985.2018-1001

摘要/Abstract

摘要： 通过研究小分子前体物对巴弗洛霉素A1生物合成的影响,寻找提高巴弗洛霉素A1发酵产量的有效方法。主要考察了不同前体物对巴弗洛霉素A1生物合成的影响,以及有效前体物的最佳添加浓度和添加时间点。结果显示,缬氨酸是巴弗洛霉素A1合成的最佳前体,36 h时添加0.2%缬氨酸,巴弗洛霉素A1产量高达285.5 mg/L,比对照组提高了78.4%。前体物的供给能显著影响巴弗洛霉素A1的生物合成,补加缬氨酸能有效提高巴弗洛霉素A1的发酵产量。

关键词: 巴弗洛霉素A1, 生物合成, 发酵, 前体

Abstract: The objective of this work is to explore an effective method of increasing bafilomycin A1 productivity via understanding the effects of small molecule precursors on bafilomycin A1 biosynthesis. The effects of different precursors on the biosynthesis of bafilomycin A1,the optimal concentration and feeding time of the effective precursor were mainly studied. As result,valine was the optimal precursor for bafilomycin A1 biosynthesis. By feeding of 0.2% valine into the fermentation broth at the 36th hour of cultivation,the bafilomycin A1 production reached 285.5 mg/L,which was 78.4% higher than that in the condition without any addition of precursor. In conclusion,feeding precursors significantly influences bafilomycin A1 biosynthesis,and the addition of valine is effective in increasing bafilomycin A1 production.

Key words: bafilomycin A1, biosynthesis, fermentation, precursor

周剑, 孙菲, 方志锴, 江红. 小分子前体物对巴弗洛霉素A1生物合成的影响[J]. 生物技术通报, 2019, 35(6): 125-130.

ZHOU Jian, SUN Fei, FANG Zhi-kai, JIANG Hong. Effects of Small Molecule Precursors on Bafilomycin A1 Biosynthesis[J]. Biotechnology Bulletin, 2019, 35(6): 125-130.

参考文献

[1] Werner G, Hagenmaier H, Albert K, et al.The structure of the bafilomycins, a new group of macrolide antibiotics[J]. Tetrahedron Letters, 1983, 24(47):5193-5196.
[2] Bowman EJ, Siebers A, Altendorf K.Bafilomycins:a class of inhibitors of membrane ATPases from microorganisms, animal cells, and plant cells[J]. Proceedings of the National Academy of Sciences of the United States of America, 1988, 85(21):7972-7976.
[3] Mauyezin C, Nagy P, Juhasz G, et al.Autophagosome-lysosome fusion is independent of V-ATPase-mediated acidification[J]. Nature Communications, 2015, 11(6):7007-7019.
[4] Gerber HP, Koehn FE, Abraham RT.The antibody-drug conjugate:an enabling modality for natural product-based cancer therapeutics[J]. Natural Product Reports, 2013, 30(5):625-39.
[5] Yuan N, Song L, Zhang S, et al.Bafilomycin A1 targets both autophagy and apoptosis pathways in pediatric B-cell acute lymphoblastic leukemia[J]. Haematologica, 2015, 100(3):345-56.
[6] Werner G, Hagenmaier H, Drautz H, et al.Metabolic products of microorganisms. 224. Bafilomycins, a new group of macrolide antibiotics. Production, isolation, chemical structure and biological activity[J]. The Journal of Antibiotics, 1984, 37(2):110-7.
[7] Seto H, Tajima I, Akao H, et al.The isolation and structures of hygrolidin amide and defumarylhygrolidin[J]. J Antibiot, 1984, 37(5):610-613.
[8] Kretschmer A, Dorgerloh M, Deeg M, et al.The structures of novel insecticidal macrolides bafilomycins D and E, and oxohygrolidin[J]. Agric Biol Chem, 1985, 49(8):2509-2511.
[9] Kim SD, Ryoo IJ, Kim CJ.Taxonomy, fermentation, isolation and characterization of a herbicidal compound, 3D5[J]. J Microbiolo Biotechnol, 1993, 3(1):57-60.
[10] Chu HY, Chen X, Jiang YE, et al.Bafilomycin A1 increases the sensitivity of tongue squamous cell carcinoma cells to cisplatin by inhibiting the lysosomal uptake of platinum ions but not autophagy[J]. Cancer Letters, 2018, 423(3):105-112.
[11] 魏刚, 苏超, 张道敬等. 海洋放线菌Y12-26代谢产物中bafilomycins分离纯化及结构鉴定[J]. 中国抗生素杂志, 2011, 36(8):571-575.
[12] 孙益, 姚瑜. 大环内酯类抗生素的菌种选育, 发酵和生物合成[J]. 国外医药:抗生素分册, 1997, 18(2):99-113.
[13] 李婷兰, 韦柳静, 范宇翔等. 奇迹束丝放线菌合成安丝菌素过程中支链氨基酸的添加效果分析[J]. 华东理工大学学报, 2013, 39(6):675-680.
[14] Lin JX, Bai LQ, Deng ZX, et al.Enhanced production of ansamitocin P-3 by addition of isobutanol in fermentation of Actinosynnema pretiosum[J]. Bioresource Technology, 2011, 102(2):1863-1868
[15] 吕伟, 庄英萍, 储炬等. 氨基酸对利用红色糖多孢菌发酵生产红霉素的产量及组分影响研究[J]. 中国抗生素杂志, 2006, 31(10):595-599.
[16] 杨莲芳, 曹健, 张中州等. 不同种类植物油对红霉素发酵的影响[J]. 食品与发酵科技, 2009, 45(4):46-48.
[17] 刘宁, 金志华, 骆健美等. 前体对纳他霉素生物合成的影响[J]. 中国抗生素杂志, 2005, 30(6):328-331.
[18] Li Z, Du L, Zhang W, et al.Complete elucidation of the late steps of bafilomycin biosynthesis in Streptomyces lohii[J]. Journal of Biological Chemistry, 2017, 292(17):7095-7104.
[19] Hwang JY, Kim SH, Oh HR, et al.Analysis of a draft genome sequence of Kitasatospora cheerisanensis KCTC 2395 producing bafilomycin antibiotics[J]. Journal of Microbiology, 2015, 53(1):84-89.
[20] 吴国峰, 李国全, 马永. 工业发酵分析[M]. 北京:化学工业出版社, 2006:11-12.
[21] 陈钧鸣, 徐玲娣. 抗生素工业分析[M]. 北京:中国医药科技出版社. 1991:109.
[22] 潘华奇, 于素亚, 胡江春, 等. 一种卡伍尔氏链霉菌及其应用:中国, 103820351B[P].2015-12-23.
[23] 杨巍民, 斯聪聪, 杨星等. 海洋放线菌Y-0117农用活性代谢产物的研究[J]. 化学与生物工程, 2013, 30(1):24-27.
[24] Yu Z, Zhao LX, Jiang CL, et al.Bafilomycins produced by an endophytic actinomycete Streptomyces sp. YIM56209[J]. The Journal of Antibiotics, 2011, 64(1):159-162.
[25] Carr G, Williams DE, Diaz-Marrero AR, et al.Bafilomycins produced in culture by Streptomyces spp. isolated from marine habitats are potent inhibitors of autophagy[J]. Journal of Natural Products, 2010, 73(3):422-427.
[26] Lee DW, BG NG, Kim BS.Increased valinomycin production in mutants of Streptomyces sp. M10 defective in bafilomycin biosynthesis and branched-chain α-keto acid dehydrogenase complex expression[J]. J Ind Microbiol Biotechnol, 2015, 42
(11):1507-1517.
[27] Zhang W, Jeffrey LF, Carlson JC, et al.Characterization of the bafilomycin biosynthetic gene cluster from Streptomyces lohii[J]. Chembiochem A European Journal of Chemical Biology, 2013, 14(3):301-306.
[28] Yoon HJ, Sun KH, Hee KS, et al.Organization and characterization of a biosynthetic gene cluster for bafilomycin from Streptomyces griseus DSM 2608[J]. Amb Express, 2013, 3(1):24.
[29] 姚永鹏, 王为善, 杨克迁. 链霉菌中高效生产聚酮化合物的研究方法及进展[J]. 微生物学报, 2016, 56(3):418-428.
[30] 李婷兰, 韦柳静, 范宇翔等. 奇迹束丝放线菌合成安丝菌素过程中支链氨基酸的添加效果分析[J]. 华东理工大学学报:自然科学版, 2013, 39(6):675-680.