Improvement of gougerotin and nikkomycin production by engineering their biosynthetic gene clusters
详细信息 查看全文
- 作者：Deyao Du (1) (2)
Yu Zhu (1) (2)
Junhong Wei (1) (2)
Yuqing Tian (1)
Guoqing Niu (1)
Huarong Tan (1) - 关键词：Promoter activity ; Nikkomycin ; Gougerotin ; Engineering ; Streptomyces
- 刊名：Applied Microbiology and Biotechnology
- 出版年：2013
- 出版时间：July 2013
- 年：2013
- 卷：97
- 期：14
- 页码：6383-6396
- 全文大小：614KB
- 参考文献：1. Bibb MJ, Janssen GR, Ward JM (1985) Cloning and analysis of the promoter region of the erythromycin resistance gene ( / ermE) of / Streptomyces erythraeus. Gene 38:215鈥?26 CrossRef
2. Clark JM, Gunther JK (1963) Gougerotin, a specific inhibitor of protein synthesis. Biochim Biophys Acta 76:636鈥?38 CrossRef
3. Dangel V, Westrich L, Smith M, Heide L, Gust B (2010) Use of an inducible promoter for antibiotic production in a heterologous host. Appl Microbiol Biotechnol 87:261鈥?69 CrossRef
4. Datsenko KA, Wanner BL (2000) One-step inactivation of chromosomal genes in / Escherichia coli K-12 using PCR products. Proc Natl Acad Sci U S A 97:6640鈥?645 CrossRef
5. Denis F, Brzezinski R (1991) An improved aminoglycoside resistance gene cassette for use in Gram-negative bacteria and / Streptomyces. FEMS Microbiol Lett 81:261鈥?64 CrossRef
6. Fiedler HP (1984) Screening for new microbial products by high-performance liquid chromatography using a photodiode array detector. J Chromatogr 316:487鈥?94 CrossRef
7. Fiedler HP, Kurth R, Langh盲rig J, Delzer J, Z盲hner H (1982) Nikkomycins: microbial inhibitors of chitin synthase. J Chem Technol Biotechnol 32:271鈥?80 CrossRef
8. Gomez-Escribano JP, Bibb MJ (2011) Engineering / Streptomyces coelicolor for heterologous expression of secondary metabolite gene clusters. Microb Biotechnol 4:207鈥?15 CrossRef
9. Guo J, Zhao J, Li L, Chen Z, Wen Y, Li J (2010) The pathway-specific regulator AveR from / Streptomyces avermitilis positively regulates avermectin production while it negatively affects oligomycin biosynthesis. Mol Genet Genomics 283:123鈥?33 CrossRef
10. Haneishi T, Arai M, Kitano N, Yamamoto S (1974) Aspiculamycin, a new cytosine nucleoside antibiotic. 3. Biological activities, in vitro and in vivo. J Antibiot 27:339鈥?42 antibiotics.27.339">CrossRef
11. Herai S, Hashimoto Y, Higashibata H, Maseda H, Ikeda H, Omura S, Kobayashi M (2004) Hyper-inducible expression system for / Streptomycetes. Proc Natl Acad Sci U S A 101:14031鈥?4035 CrossRef
12. Jung WS, Jeong SJ, Park SR, Choi CY, Park BC, Park JW, Yoon YJ (2008) Enhanced heterologous production of desosaminyl macrolides and their hydroxylated derivatives by overexpression of the / pikD regulatory gene in / Streptomyces venezuelae. Appl Environ Microbiol 74:1972鈥?979 CrossRef
13. Kieser T, Bibb MJ, Buttner MJ, Chater KF, Hopwood DA (2000) Practical / Streptomyces genetics. The John Innes Foundation, Norwich
14. Kondo F, Kitano N, Domon H, Arai M, Haneishi T (1974) Aspiculamycin, a new cytosine nucleoside antibiotic. IV. Antimycoplasma activity of aspiculamycin in vitro and in vivo. J Antibiot 27:529鈥?34 antibiotics.27.529">CrossRef
15. Labes G, Bibb M, Wohlleben W (1997) Isolation and characterization of a strong promoter element from the / Streptomyces ghanaensis phage I19 using the gentamicin resistance gene ( / aacC1) of Tn 1696 as reporter. Microbiology 143:1503鈥?512 CrossRef
16. Lacal JC, V谩zquez D, Fernandez-Sousa JM, Carrasco L (1980) Antibiotics that specifically block translation in virus-infected cells. J Antibiot 33:441鈥?46 antibiotics.33.441">CrossRef
17. Li Y, Ling H, Li W, Tan H (2005) Improvement of nikkomycin production by enhanced copy of / sanU and / sanV in / Streptomyces ansochromogenes and characterization of a novel glutamate mutase encoded by / sanU and / sanV. Metab Eng 7:165鈥?73 CrossRef
18. Li R, Xie Z, Tian Y, Yang H, Chen W, You D, Liu G, Deng Z, Tan H (2009) / polR, a pathway-specific transcriptional regulatory gene, positively controls polyoxin biosynthesis in / Streptomyces cacaoi subsp. / asoensis. Microbiology 155:1819鈥?831 CrossRef
19. Liao G, Li J, Li L, Yang H, Tian Y, Tan H (2009) Selectively improving nikkomycin Z production by blocking the imidazolone biosynthetic pathway of nikkomycin X and uracil feeding in / Streptomyces ansochromogenes. Microb Cell Fact 8:61 CrossRef
20. Liao G, Li J, Li L, Yang H, Tian Y, Tan H (2010) Cloning, reassembling and integration of the entire nikkomycin biosynthetic gene cluster into / Streptomyces ansochromogenes lead to an improved nikkomycin production. Microb Cell Fact 9:6 CrossRef
21. Liu G, Tian Y, Yang H, Tan H (2005) A pathway-specific transcriptional regulatory gene for nikkomycin biosynthesis in / Streptomyces ansochromogenes that also influences colony development. Mol Microbiol 55:1855鈥?866 CrossRef
22. Medema MH, Alam MT, Breitling R, Takano E (2011) The future of industrial antibiotic production: from random mutagenesis to synthetic biology. Bioeng Bugs 2:230鈥?33 CrossRef
23. Niu G, Li L, Wei J, Tan H (2013) Cloning, heterologous expression, and characterization of the gene cluster required for gougerotin biosynthesis. Chem Biol 20:34鈥?4 CrossRef
24. Paget MS, Chamberlin L, Atrih A, Foster SJ, Buttner MJ (1999) Evidence that the extracytoplasmic function sigma factor 蟽E is required for normal cell wall structure in / Streptomyces coelicolor A3(2). J Bacteriol 181:204鈥?11
25. Pan Y, Liu G, Yang H, Tian Y, Tan H (2009) The pleiotropic regulator AdpA-L directly controls the pathway-specific activator of nikkomycin biosynthesis in / Streptomyces ansochromogenes. Mol Microbiol 72:710鈥?23 CrossRef
26. Rodr铆guez-Garc铆a A, Combes P, P茅rez-Redondo R, Smith MC, Smith MC (2005) Natural and synthetic tetracycline-inducible promoters for use in the antibiotic-producing bacteria / Streptomyces. Nucleic Acids Res 33:e87 CrossRef
27. Sambrook J, Russell DW (2001) Molecular cloning: a laboratory manual. Cold spring harbor laboratory, Cold Spring Harbor
28. Seghezzi N, Amar P, Koebmann B, Jensen PR, Virolle MJ (2011) The construction of a library of synthetic promoters revealed some specific features of strong / Streptomyces promoters. Appl Microbiol Biotechnol 90:615鈥?23 CrossRef
29. Takano E, White J, Thompson CJ, Bibb MJ (1995) Construction of thiostrepton-inducible, high-copy-number expression vectors for use in / Streptomyces spp. Gene 166:133鈥?37 CrossRef
30. Wang G, Tan H (2004) Enhanced production of nikkomycin X by over-expression of SanO, a non-ribosomal peptide synthetase in / Streptomyces ansochromogenes. Biotechnol Lett 26:229鈥?33 CrossRef
31. Wang SL, Fan KQ, Yang X, Lin ZX, Xu XP, Yang KQ (2008) CabC, an EF-hand calcium-binding protein, is involved in Ca2+-mediated regulation of spore germination and aerial hypha formation in / Streptomyces coelicolor. J Bacteriol 190:4061鈥?068 CrossRef
32. Yuan T, Yin C, Zhu C, Zhu B, Hu Y (2011) Improvement of antibiotic productivity by knock-out of / dauW in / Streptomyces coeruleobidus. Microbiol Res 166:539鈥?47 CrossRef
33. Zeng H, Tan H, Li J (2002) Cloning and function of / sanQ: a gene involved in nikkomycin biosynthesis of / Streptomyces ansochromogenes. Curr Microbiol 45:175鈥?79 CrossRef - 作者单位：Deyao Du (1) (2)
Yu Zhu (1) (2)
Junhong Wei (1) (2)
Yuqing Tian (1)
Guoqing Niu (1)
Huarong Tan (1)
1. State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China
2. Graduate School of Chinese Academy of Sciences, Beijing, 100039, China
文摘
Nikkomycins and gougerotin are peptidyl nucleoside antibiotics with broad biological activities. The nikkomycin biosynthetic gene cluster comprises one pathway-specific regulatory gene (sanG) and 21 structural genes, whereas the gene cluster for gougerotin biosynthesis includes one putative regulatory gene, one major facilitator superfamily transporter gene, and 13 structural genes. In the present study, we introduced sanG driven by six different promoters into Streptomyces ansochromogenes TH322. Nikkomycin production was increased significantly with the highest increase in engineered strain harboring hrdB promoter-driven sanG. In the meantime, we replaced the native promoter of key structural genes in the gougerotin (gou) gene cluster with the hrdB promoters. The heterologous producer Streptomyces coelicolor M1146 harboring the modified gene cluster produced gougerotin up to 10-fold more than strains carrying the unmodified cluster. Therefore, genetic manipulations of genes involved in antibiotics biosynthesis with the constitutive hrdB promoter present a robust, easy-to-use system generally useful for the improvement of antibiotics production in Streptomyces.