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Effects of S-adenosylmethionine on production of secondary metabolites in Streptomyces diastatochromogenes 1628

S-腺苷甲硫氨酸对淀粉酶产色链霉菌1628次级代谢产物产量的影响

概要

目的

考察S-腺苷甲硫氨酸(SAM)对淀粉酶产色链霉菌(Streptomyces diastatochromogenes)1628次级代谢产物产量的影响.

创新点

SAM是甲基的重要供体, 可为次级代谢产物提供前体, 同时也可以作为信号增强次级代谢产物合成基因的表达. 因此, 本研究首次探究了SAM与S. diastatochromogenes 1628次级代谢产物合成的相关性.

方法

S. diastatochromogenes 1628为对象, 通过体外添加SAM以及在S. diastatochromogenes 1628体内过表达、 敲除和回补SAM编码基因metKsd, 考察S. diastatochromogenes 1628次级代谢产物产量的变化.

结论

由于渗透性差, 外源添加SAM对S. diastatochromogenes 1628合成次级代谢产物(丰加霉素和三种四烯大环内酯类抗生素: 四霉素A、 四霉素P和四烯菌素B)没有影响; 敲除、 回补和过表达基因metKsd证实增加胞内SAM可提高S. diastatochromogenes 1628三种四烯大环内酯类抗生素的产量, 且可促进四烯大环内酯类化合物合成关键基因的表达, 而胞内SAM浓度的变化对丰加霉素的产量和及其关键基因的表达均无明显影响.

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References

  1. Battaglia U, Long JE, Searle MS, et al., 2011. 7-Deazapurine biosynthesis: NMR study of toyocamycin biosynthesis in Streptomyces rimosus using 2-13C-7-15N-adenine. Org Biomol Chem, 9(7):2227–2232. https://doi.org/10.1039/c0ob01054e

    CAS  Article  Google Scholar 

  2. Cao B, Yao F, Zheng XQ, et al., 2012. Genome mining of the biosynthetic gene cluster of the polyene macrolide antibiotic tetramycin and characterization of a P450 monooxygenase involved in the hydroxylation of the tetramycin B polyol segment. ChemBioChem, 13(15):2234–2242. https://doi.org/10.1002/cbic.201200402

    CAS  Article  Google Scholar 

  3. Cui H, Ni XP, Shao W, et al., 2015. Functional manipulations of the tetramycin positive regulatory gene ttmRIV to enhance the production of tetramycin A and nystatin A1 in Streptomyces ahygroscopicus. J Ind Microbiol Biotechnol, 42(9):1273–1282. https://doi.org/10.1007/s10295-015-1660-3

    CAS  Article  Google Scholar 

  4. Cui H, Ni XP, Liu SJ, et al., 2016. Characterization of three positive regulators for tetramycin biosynthesis in Streptomyces ahygroscopicus. FEMS Microbiol Lett, 363(12): fnw109. https://doi.org/10.1093/femsle/fnw109

    Article  Google Scholar 

  5. Fan JX, Song Y, Tang G, et al., 2020. Substantial improvement of tetraene macrolide production in Streptomyces diastatochromogenes by cumulative drug resistance mutations. PLoS ONE, 15(5):e0232927. https://doi.org/10.1371/journal.pone.0232927

    CAS  Article  Google Scholar 

  6. Gu YY, Wang XM, Chao Y, et al., 2016. Effects of chromosomal integration of the Vitreoscilla hemoglobin gene (vgb) and S-adenosylmethionine synthetase gene (metK) on ε-poly-l-lysine synthesis in Streptomyces albulus NK660. Appl Biochem Biotechnol, 178(7):1445–1457. https://doi.org/10.1007/s12010-015-1958-7

    CAS  Article  Google Scholar 

  7. Huh JH, Kim DJ, Zhao XQ, et al., 2004. Corrigendum to “Widespread activation of antibiotic biosynthesis by S-adenosylmethionine in streptomycetes” [FEMS Microbiol Lett. 238 (2004) 439–447]. FEMS Microbiol Lett, 238(2):245. https://doi.org/10.1016/j.femsle.2004.08.009

    Article  Google Scholar 

  8. Kim DJ, Huh JH, Yang YY, et al., 2003. Accumulation of S-adenosyl-l-methionine enhances production of actinorhodin but inhibits sporulation in Streptomyces lividans TK23. J Bacteriol, 185(2):592–600. https://doi.org/10.1128/jb.185.2.592-600.2003

    CAS  Article  Google Scholar 

  9. Li SS, Li ZL, Pang S, et al., 2021. Coordinating precursor supply for pharmaceutical polyketide production in Streptomyces. Curr Opin Biotechnol, 69:26–34. https://doi.org/10.1016/j.copbio.2020.11.006

    CAS  Article  Google Scholar 

  10. Liao ZJ, Song ZQ, Xu J, et al., 2020. Identification of a gene from Streptomyces rimosus M527 negatively affecting rimocidin biosynthesis and morphological differentiation. Appl Microbiol Biotechnol, 104(23):10191–10202. https://doi.org/10.1007/s00253-020-10955-8

    CAS  Article  Google Scholar 

  11. Liu G, Chater KF, Chandra G, et al., 2013. Molecular regulation of antibiotic biosynthesis in Streptomyces. Microbiol Mol Biol Rev, 77(1):112–143. https://doi.org/10.1128/MMBR.00054-12

    CAS  Article  Google Scholar 

  12. Liu Q, Lin Q, Li XY, et al., 2020. Construction and application of a “superplasmid” for enhanced production of antibiotics. Appl Microbiol Biotechnol, 104(4):1647–1660. https://doi.org/10.1007/s00253-019-10283-6

    CAS  Article  Google Scholar 

  13. Ma Z, Liu JX, Bechthold A, et al., 2014a. Development of intergeneric conjugal gene transfer system in Streptomyces diastatochromogenes 1628 and its application for improvement of toyocamycin production. Curr Microbiol, 68(2):180–185. https://doi.org/10.1007/s00284-013-0461-z

    CAS  Article  Google Scholar 

  14. Ma Z, Tao LB, Bechthold A, et al., 2014b. Overexpression of ribosome recycling factor is responsible for improvement of nucleotide antibiotic-toyocamycin in Streptomyces diastatochromogenes 1628. Appl Microbiol Biotechnol, 98(11):5051–5058. https://doi.org/10.1007/s00253-014-5573-2

    CAS  Article  Google Scholar 

  15. Ma Z, Luo S, Xu XH, et al., 2016. Characterization of representative rpoB gene mutations leading to a significant change in toyocamycin production of Streptomyces diastatochromogenes 1628. J Ind Microbiol Biotechnol, 43(4): 463–471. https://doi.org/10.1007/s10295-015-1732-4

    CAS  Article  Google Scholar 

  16. Ma Z, Hu YF, Liao ZJ, et al., 2020. Cloning and overexpression of the toy cluster for titer improvement of toyocamycin in Streptomyces diastatochromogenes. Front Microbiol, 11: 2074. https://doi.org/10.3389/fmicb.2020.02074

    Article  Google Scholar 

  17. Maharjan S, Oh TJ, Lee HC, et al., 2008. Heterologous expression of metK1-sp and afsR-sp in Streptomyces venezuelae for the production of pikromycin. Biotechnol Lett, 30(9):1621–1626. https://doi.org/10.1007/s10529-008-9735-0

    CAS  Article  Google Scholar 

  18. McCarty RM, Bandarian V, 2008. Deciphering deazapurine biosynthesis: pathway for pyrrolopyrimidine nucleosides toyocamycin and sangivamycin. Chem Biol, 15(8):790–798. https://doi.org/10.1016/j.chembiol.2008.07.012

    CAS  Article  Google Scholar 

  19. Niu GQ, Chater KF, Tian YQ, et al., 2016. Specialised metabolites regulating antibiotic biosynthesis in Streptomyces spp. FEMS Microbiol Rev, 40(4):554–573. https://doi.org/10.1093/femsre/fuw012

    CAS  Article  Google Scholar 

  20. Oh TJ, Niraula NP, Liou K, et al., 2010. Identification of the duplicated genes for S-adenosyl-l-methionine synthetase (metK1-sp and metK2-sp) in Streptomyces peucetius var. caesius ATCC 27952. J Appl Microbiol, 109(2):398–407. https://doi.org/10.1111/j.1365-2672.2010.04688.x

    CAS  Article  Google Scholar 

  21. Okamoto S, Lezhava A, Hosaka T, et al., 2003. Enhanced expression of S-adenosylmethionine synthetase causes overproduction of actinorhodin in Streptomyces coelicolor A3(2). J Bacteriol, 185(2):601–609. https://doi.org/10.1128/jb.185.2.601-609.2003

    CAS  Article  Google Scholar 

  22. Park HS, Shin SK, Yang YY, et al., 2005. Accumulation of S-adenosylmethionine induced oligopeptide transporters including BldK to regulate differentiation events in Streptomyces coelicolor M145. FEMS Microbiol Lett, 249(2):199–206. https://doi.org/10.1016/j.femsle.2005.05.047

    CAS  Article  Google Scholar 

  23. Ren J, Cui YQ, Zhang F, et al., 2014. Enhancement of nystatin production by redirecting precursor fluxes after disruption of the tetramycin gene from Streptomyces ahygroscopicus. Microbiol Res, 169(7–8):602–608. https://doi.org/10.1016/j.micres.2013.09.017

    CAS  Article  Google Scholar 

  24. Sheng Y, Ou YX, Hu XJ, et al., 2020. Generation of tetramycin B derivative with improved pharmacological property based on pathway engineering. Appl Microbiol Biotechnol, 104(6):2561–2573. https://doi.org/10.1007/s00253-020-10391-8

    CAS  Article  Google Scholar 

  25. Shentu X, Li DT, Xu JF, et al., 2016. Effects of fungicides on the yeast-like symbiotes and their host, Nilaparvata lugens Stål (Hemiptera: Delphacidae). Pestic Biochem Physiol, 128:16–21. https://doi.org/10.1016/j.pestbp.2015.10.010

    CAS  Article  Google Scholar 

  26. Song ZQ, Liao ZJ, Hu YF, et al., 2019. Development and optimization of an intergeneric conjugation system and analysis of promoter activity in Streptomyces rimosus M527. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 20(11):891–900. https://doi.org/10.1631/jzus.B1900270

    CAS  Article  Google Scholar 

  27. Song ZQ, Ma Z, Bechthold A, et al., 2020. Effects of addition of elicitors on rimocidin biosynthesis in Streptomyces rimosus M527. Appl Microbiol Biotechnol, 104(10):4445–4455. https://doi.org/10.1007/s00253-020-10565-4

    CAS  Article  Google Scholar 

  28. Tian PP, Cao P, Hu D, et al., 2017. Comparative metabolomics reveals the mechanism of avermectin production enhancement by S-adenosylmethionine. J Ind Microbiol Biotechnol, 44(4–5):595–604. https://doi.org/10.1007/s10295-016-1883-y

    CAS  Article  Google Scholar 

  29. Wang T, Bai LQ, Zhu DQ, et al., 2012. Enhancing macrolide production in Streptomyces by coexpressing three heterologous genes. Enzyme Microb Technol, 50(1):5–9. https://doi.org/10.1016/j.enzmictec.2011.09.014

    CAS  Article  Google Scholar 

  30. Wang Y, Boghigian BA, Pfeifer BA, 2007. Improving heterologous polyketide production in Escherichia coli by overexpression of an S-adenosylmethionine synthetase gene. Appl Microbiol Biotechnol, 77(2):367–373. https://doi.org/10.1007/s00253-007-1172-9

    CAS  Article  Google Scholar 

  31. Xu J, Song ZQ, Xu XH, et al., 2019. ToyA, a positive pathway-specific regulator for toyocamycin biosynthesis in Streptomyces diastatochromogenes 1628. Appl Microbiol Biotechnol, 103(17):7071–7084. https://doi.org/10.1007/s00253-019-09959-w

    CAS  Article  Google Scholar 

  32. Xu YR, Tan GQ, Ke ML, et al., 2018. Enhanced lincomycin production by co-overexpression of metK1 and metK2 in Streptomyces lincolnensis. J Ind Microbiol Biotechnol, 45(5):345–355. https://doi.org/10.1007/s10295-018-2029-1

    CAS  Article  Google Scholar 

  33. Yin HZ, Wang WS, Fan KQ, et al., 2019. Regulatory perspective of antibiotic biosynthesis in Streptomyces. Sci China Life Sci, 62(5):698–700. https://doi.org/10.1007/s11427-019-9497-5

    Article  Google Scholar 

  34. Zhang XC, Fen MQ, Shi XL, et al., 2008. Overexpression of yeast S-adenosylmethionine synthetase metK in Streptomyces actuosus leads to increased production of nosiheptide. Appl Microbiol Biotechnol, 78(6):991–995. https://doi.org/10.1007/s00253-008-1394-5

    CAS  Article  Google Scholar 

  35. Zhao XH, Zhong LJ, Zhang QH, et al., 2010. Effect of tetramycin on mycelial growth and spore germination of rice blast pathogen. J Microbiol, 30(2):43–45 (in Chinese). https://doi.org/10.3969/j.issn.1005-7021.2010.02.009

    Google Scholar 

  36. Zhao XQ, Gust B, Heide L, 2010. S-adenosylmethionine (SAM) and antibiotic biosynthesis: effect of external addition of SAM and of overexpression of SAM biosynthesis genes on novobiocin production in Streptomyces. Arch Microbiol, 192(4):289–297. https://doi.org/10.1007/s00203-010-0548-x

    CAS  Article  Google Scholar 

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Acknowledgments

This study was supported by the Excellent Youth Fund of Zhejiang Province, China (No. LR17C140002).

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Authors

Contributions

Yefeng HU, Juan WANG, and Jie XU conducted experiments. Yefeng HU wrote the original draft. Zheng MA designed the experiments and wrote this article. Andreas BECHTHOLD and Xiaoping YU gave some good suggestions on the revision of the manuscript, polished English and checked the final version. All authors have read and approved the final manuscript and, therefore, have full access to all the data in the study and take responsibility for the integrity and security of the data.

Corresponding author

Correspondence to Zheng Ma.

Ethics declarations

Yefeng HU, Juan WANG, Jie XU, Zheng MA, Andreas BECHTHOLD, and Xiaoping YU declare that they have no conflict of interest.

This article does not involve any studies with human or animal subjects.

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Detailed methods are provided in the electronic supplementary materials of this paper.

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Hu, Y., Wang, J., Xu, J. et al. Effects of S-adenosylmethionine on production of secondary metabolites in Streptomyces diastatochromogenes 1628. J. Zhejiang Univ. Sci. B 22, 767–773 (2021). https://doi.org/10.1631/jzus.B2100115

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关键词

  • 淀粉酶产色链霉菌1628
  • S-腺苷甲硫氨酸
  • MetK
  • 丰加霉素
  • 四烯大环内酯类