Skip to main content

Advertisement

SpringerLink
Log in

Complete Genome Sequence of Actinosynnema pretiosum X47, An Industrial Strain that Produces the Antibiotic Ansamitocin AP-3

  • Letter to the Editor
  • Published:
Current Microbiology Aims and scope Submit manuscript

Abstract

Ansamitocins are extraordinarily potent antitumor agents. Ansamitocin P-3 (AP-3), which is produced by Actinosynnema pretiosum, has been developed as a cytotoxic drug for breast cancer. Despite its importance, AP-3 is of limited applicability because of the low production yield. A. pretiosum strain X47 was developed from A. pretiosum ATCC 31565 by mutation breeding and shows a relatively high AP-3 yield. Here, we analyzed the A. pretiosum X47 genome, which is ~8.13 Mb in length with 6693 coding sequences, 58 tRNA genes, and 15 rRNA genes. The DNA sequence of the ansamitocin biosynthetic gene cluster is highly similar to that of the corresponding cluster in A. pretiosum ATCC 31565, with 99.9% identity. However, RT-qPCR analysis showed that the expression levels of ansamitocin biosynthetic genes were significantly increased in X47 compared with the levels in the wild-type strain, consistent with the higher yield of AP-3 in X47. The annotated complete genome sequence of this strain will facilitate understanding the molecular mechanisms of ansamitocin biosynthesis and regulation in A. pretiosum and help further genetic engineering studies to enhance the production of AP-3.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

References

  1. Amiri-Kordestani L, Blumenthal GM, Xu QC, Zhang L, Tang SW, Ha L, Weinberg WC, Chi B, Candau-Chacon R, Hughes P, Russell AM, Miksinski SP, Chen XH, McGuinn WD, Palmby T, Schrieber SJ, Liu Q, Wang J, Song P, Mehrotra N, Skarupa L, Clouse K, Al-Hakim A, Sridhara R, Ibrahim A, Justice R, Pazdur R, Cortazar P (2014) FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer. Clin Cancer Res 20(17):4436–4441. https://doi.org/10.1158/1078-0432.CCR-14-0012

    Article  CAS  PubMed  Google Scholar 

  2. Blin K, Medema MH, Kottmann R, Lee SY, Weber T (2017) The antiSMASH database, a comprehensive database of microbial secondary metabolite biosynthetic gene clusters. Nucleic Acids Res 45(D1):D555–D559. https://doi.org/10.1093/nar/gkw960

    Article  CAS  PubMed  Google Scholar 

  3. Brettin T, Davis JJ, Disz T, Edwards RA, Gerdes S, Olsen GJ, Olson R, Overbeek R, Parrello B, Pusch GD, Shukla M, Thomason JA 3rd, Stevens R, Vonstein V, Wattam AR, Xia F (2015) RASTtk: a modular and extensible implementation of the RAST algorithm for building custom annotation pipelines and annotating batches of genomes. Sci Rep 5:8365. https://doi.org/10.1038/srep08365

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Cassady JM, Chan KK, Floss HG, Leistner E (2004) Recent developments in the maytansinoid antitumor agents. Chem Pharm Bull 52(1):1–26. https://doi.org/10.1248/cpb.52.1

    Article  CAS  Google Scholar 

  5. Coil D, Jospin G, Darling AE (2015) A5-miseq: an updated pipeline to assemble microbial genomes from Illumina MiSeq data. Bioinformatics 31(4):587–589. https://doi.org/10.1093/bioinformatics/btu661

    Article  CAS  PubMed  Google Scholar 

  6. Darling AC, Mau B, Blattner FR, Perna NT (2004) Mauve: multiple alignment of conserved genomic sequence with rearrangements. Genome Res 14(7):1394–1403. https://doi.org/10.1101/gr.2289704

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Erickson HK, Lambert JM (2012) ADME of antibody-maytansinoid conjugates. AAPS J 14(4):799–805. https://doi.org/10.1208/s12248-012-9386-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Fan Y, Hu F, Wei L, Bai L, Hua Q (2016) Effects of modulation of pentose-phosphate pathway on biosynthesis of ansamitocins in Actinosynnema pretiosum. J Biotechnol 230:3–10. https://doi.org/10.1016/j.jbiotec.2016.05.010

    Article  CAS  PubMed  Google Scholar 

  9. Galperin MY, Makarova KS, Wolf YI, Koonin EV (2015) Expanded microbial genome coverage and improved protein family annotation in the COG database. Nucleic Acids Res 43:D261–D269. https://doi.org/10.1093/nar/gku1223

    Article  CAS  PubMed  Google Scholar 

  10. Gao Y, Fan Y, Nambou K, Wei L, Liu Z, Imanaka T, Hua Q (2014) Enhancement of ansamitocin P-3 production in Actinosynnema pretiosum by a synergistic effect of glycerol and glucose. J Ind Microbiol Biotechnol 41(1):143–152. https://doi.org/10.1007/s10295-013-1374-3

    Article  CAS  PubMed  Google Scholar 

  11. Higashide E, Asai M, Ootsu K, Tanida S, Kozai Y, Hasegawa T, Kishi T, Sugino Y, Yoneda M (1977) Ansamitocin, a group of novel maytansinoid antibiotics with antitumour properties from Nocardia. Nature 270(5639):721–722. https://doi.org/10.1038/270721a0

    Article  CAS  PubMed  Google Scholar 

  12. Koren S, Walenz BP, Berlin K, Miller JR, Bergman NH, Phillippy AM (2017) Canu: scalable and accurate long-read assembly via adaptive k-mer weighting and repeat separation. Genome Res 27(5):722–736. https://doi.org/10.1101/gr.215087.116

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Land M, Lapidus A, Mayilraj S, Chen F, Copeland A, Del Rio TG, Nolan M, Lucas S, Tice H, Cheng JF, Chertkov O, Bruce D, Goodwin L, Pitluck S, Rohde M, Goker M, Pati A, Ivanova N, Mavromatis K, Chen A, Palaniappan K, Hauser L, Chang YJ, Jeffries CC, Brettin T, Detter JC, Han C, Chain P, Tindall BJ, Bristow J, Eisen JA, Markowitz V, Hugenholtz P, Kyrpides NC, Klenk HP (2009) Complete genome sequence of Actinosynnema mirum type strain (101). Stand Genomic Sci 1(1):46–53. https://doi.org/10.4056/sigs.21137

    Article  PubMed  PubMed Central  Google Scholar 

  14. Marcais G, Delcher AL, Phillippy AM, Coston R, Salzberg SL, Zimin A (2018) MUMmer4: a fast and versatile genome alignment system. PLoS Comput Biol 14(1):e1005944. https://doi.org/10.1371/journal.pcbi.1005944

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Spiteller P, Bai L, Shang G, Carroll BJ, Yu TW, Floss HG (2003) The post-polyketide synthase modification steps in the biosynthesis of the antitumor agent ansamitocin by Actinosynnema pretiosum. J Am Chem Soc 125(47):14236–14237. https://doi.org/10.1021/ja038166y

    Article  CAS  PubMed  Google Scholar 

  16. Walker BJ, Abeel T, Shea T, Priest M, Abouelliel A, Sakthikumar S, Cuomo CA, Zeng Q, Wortman J, Young SK, Earl AM (2014) Pilon: an integrated tool for comprehensive microbial variant detection and genome assembly improvement. PLoS ONE 9(11):e112963. https://doi.org/10.1371/journal.pone.0112963

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Watanabe K, Okuda T, Yokose K, Furumai T, Maruyama HB (1983) Actinosynnema mirum, a new producer of nocardicin antibiotics. J Antibiot 36(3):321–324. https://doi.org/10.7164/antibiotics.36.321

    Article  CAS  Google Scholar 

  18. Yu TW, Bai L, Clade D, Hoffmann D, Toelzer S, Trinh KQ, Xu J, Moss SJ, Leistner E, Floss HG (2002) The biosynthetic gene cluster of the maytansinoid antitumor agent ansamitocin from Actinosynnema pretiosum. Proc Natl Acad Sci USA 99(12):7968–7973. https://doi.org/10.1073/pnas.092697199

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Yu Z, Ma Y, Zhong W, Qiu J, Li J (2017) Comparative genomics of Methanopyrus sp. SNP6 and KOL6 revealing genomic regions of plasticity implicated in extremely thermophilic profiles. Front Microbiol 8:1278. https://doi.org/10.3389/fmicb.2017.01278

    Article  PubMed  PubMed Central  Google Scholar 

  20. Zhang P, Wu L, Zhu Y, Liu M, Wang Y, Cao G, Chen XL, Tao M, Pang X (2017) Deletion of MtrA inhibits cellular development of Streptomyces coelicolor and alters expression of developmental regulatory genes. Front Microbiol 8:2013. https://doi.org/10.3389/fmicb.2017.02013

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This research was supported by the National Natural Science Foundation of China (No. 31700065), Shandong Provincial Natural Science Foundation (No. ZR2017BC040), and the Innovation Project of the Shandong Academy of Medical Sciences.

Author information

Author notes

  1. Chuanqing Zhong and Gongli Zong have contributed equally.

Authors and Affiliations

  1. School of Municipal and Environmental Engineering, Shandong Jianzhu University, Jinan, China

    Chuanqing Zhong

  2. Shandong Medicinal Biotechnology Center, Shandong Academy of Medical Sciences, Jinan, China

    Gongli Zong, Jiafang Fu & Guangxiang Cao

  3. College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, China

    Shulan Qian & Jun Li

  4. State Key Laboratory of Microbial Technology, Shandong University, Jinan, China

    Meng Liu & Peipei Zhang

Authors
  1. Chuanqing Zhong
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gongli Zong
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shulan Qian
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Meng Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jiafang Fu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Peipei Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jun Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Guangxiang Cao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Guangxiang Cao.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 191 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhong, C., Zong, G., Qian, S. et al. Complete Genome Sequence of Actinosynnema pretiosum X47, An Industrial Strain that Produces the Antibiotic Ansamitocin AP-3. Curr Microbiol 76, 954–958 (2019). https://doi.org/10.1007/s00284-018-1521-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00284-018-1521-1

Search

Navigation