Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Albumycin, a new isoindolequinone from Streptomyces albus J1074 harboring the fluostatin biosynthetic gene cluster

The Journal of Antibiotics volume 72, pages 311–315 (2019)Cite this article

Subjects

Abstract

Heterologous expression of the fluostatin biosynthetic gene cluster from the marine-derived Micromonospora rosaria SCSIO N160 in Streptomyces albus J1074 led to the isolation of a novel isoindolequinone albumycin (1) and a known isoquinolinequinone mansouramycin A (2). The structure of 1 was elucidated on the basis of detailed 1D and 2D NMR spectroscopic analysis. Mansouramycin A (2) is active against methicillin-resistant Staphylococcus aureus ATCC 43300, with a MIC of 8 μg ml−1, while albumycin (1) displayed negligible antibacterial activities. This study represents another example of activation of secondary metabolites that are non-relevant to the heterologously introduced biosynthetic gene cluster in a bacterial host.

Marine-derived actinomycetes are an important source of a variety of novel natural products with comprehensive biological activities. In recent years, the rediscovery rate for known compounds from marine-derived actinomycetes is increasing [1]. Thus, novel methods have been developed for the rapid dereplication of known natural products and targeted identification of novel compounds, such as the imaging mass spectrometry method [2], the strain prioritization by real-time polymerase chain reaction [3], the resistance gene-guided genome mining [4], the bioinformatics-guided search strategy [5], and the CRISPR/Cas9-based editing-directed activation of silent clusters [6]. Nevertheless, heterologous expression is still thought as a promising tool for natural products studies and has been widely applied to enable the discovery of new compounds from silent biosynthetic gene clusters, and to improve the yield of natural products [7].

This is a preview of subscription content, access via your institution

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

Buy

All prices are NET prices.

Fig. 1
Fig. 2

References

  1. Dashti Y, Grkovic T, Abdelmohsen U, Hentschel U, Quinn R. Production of induced secondary metabolites by a co-culture of sponge-associated Actinomycetes, Actinokineospora sp. EG49 and Nocardiopsis sp. RV163. Mar Drugs. 2014;12:3046–59.

    Article  Google Scholar 

  2. Esquenazi E, Yang Y-L, Watrous J, Gerwick WH, Dorrestein PC. Imaging mass spectrometry of natural products. Nat Prod Rep. 2009;26:1521–34.

    Article  CAS  Google Scholar 

  3. Hindra, Huang T, Yang D, Rudolf JD, Xie P, Xie G, et al. Strain prioritization for natural product discovery by a high-throughput real-time PCR method. J Nat Prod. 2014;77:2296–303.

    Article  CAS  Google Scholar 

  4. Yan Y, Liu Q, Zang X, Yuan S, Bat-Erdene U, Nguyen C, et al. Resistance-gene-directed discovery of a natural-product herbicide with a new mode of action. Nature. 2018;559:415–8.

    Article  CAS  Google Scholar 

  5. Bushin LB, Clark KA, Pelczer I, Seyedsayamdost MR. Charting an unexplored streptococcal biosynthetic landscape reveals a unique peptide cyclization motif. J Am Chem Soc. 2018. https://doi.org/10.1021/jacs.8b10266.

    Article  CAS  Google Scholar 

  6. Zhang MM, Wong FT, Wang Y, Luo S, Lim YH, Heng E, et al. CRISPR-Cas9 strategy for activation of silent Streptomyces biosynthetic gene clusters. Nat Chem Biol. 2017;13:607–9.

    Article  CAS  Google Scholar 

  7. Yang D, Zhu X, Wu X, Feng Z, Huang L, Shen B, et al. Titer improvement of iso-migrastatin in selected heterologous Streptomyces hosts and related analysis of mRNA expression by quantitative RT–PCR. Appl Microbiol Biotechnol. 2011;89:1709–19.

    Article  CAS  Google Scholar 

  8. Yang C, Huang C, Zhang W, Zhu Y, Zhang C. Heterologous expression of fluostatin gene cluster leads to a bioactive heterodimer. Org Lett. 2015;17:5324–7.

    Article  CAS  Google Scholar 

  9. Huang C, Yang C, Zhang W, Zhang L, De BC, Zhu Y, et al. Molecular basis of dimer formation during the biosynthesis of benzofluorene-containing atypical angucyclines. Nat Commun. 2018;9:2088.

    Article  Google Scholar 

  10. Huang C, Yang C, Zhu Y, Zhang W, Yuan C, Zhang C. Marine bacterial aromatic polyketides from host-dependent heterologous expression and fungal mode of cyclization. Front Chem. 2018;6:528.

    Article  Google Scholar 

  11. Mahmoud KAS. Nafisamycin, cyclisation product of a new enediyne precursor, highly cytotoxic mansouramycins, karamomycins possessing a novel heterocyclic skeleton and further unusual secondary metabolites from terrestrial and marine bacteria. Ph.D. Thesis, Georg-August-Universität zu Göttingen, Germany, 2008.

  12. Hawas UW, Shaaban M, Shaaban KA, Speitling M, Maier A, Kelter G, et al. Mansouramycins A−D, cytotoxic isoquinolinequinones from a marine Streptomycete. J Nat Prod. 2009;72:2120–4.

    Article  CAS  Google Scholar 

  13. Xu F, Nazari B, Moon K, Bushin LB, Seyedsayamdost MR. Discovery of a cryptic antifungal compound from Streptomyces albus J1074 using high-throughput elicitor screens. J Am Chem Soc. 2017;139:9203–12.

    Article  CAS  Google Scholar 

  14. Karlsson C, Jämstorp E, Strømme M, Sjödin M. Computational electrochemistry study of 16 isoindole-4,7-diones as candidates for organic cathode materials. J Phys Chem C. 2012;116:3793–801.

    Article  CAS  Google Scholar 

  15. Zhang W, Liu Z, Li S, Lu Y, Chen Y, Zhang H, et al. Fluostatins I-K from the South China Sea-derived Micromonospora rosaria SCSIO N160. J Nat Prod. 2012;75:1937–43.

    Article  CAS  Google Scholar 

  16. Zhang W, Yang C, Huang C, Zhang L, Zhang H, Zhang Q, et al. Pyrazolofluostatins A–C, pyrazole-fused benzo[a]fluorenes from South China Sea-derived Micromonospora rosaria SCSIO N160. Org Lett. 2017;19:592–5.

    Article  CAS  Google Scholar 

  17. Braña AF, Rodríguez M, Pahari P, Rohr J, García LA, Blanco G. Activation and silencing of secondary metabolites in Streptomyces albus and Streptomyces lividans after transformation with cosmids containing the thienamycin gene cluster from Streptomyces cattleya. Arch Microbiol. 2014;196:345–55.

    Article  Google Scholar 

  18. Olano C, García I, González A, Rodriguez M, Rozas D, Rubio J, et al. Activation and identification of five clusters for secondary metabolites in Streptomyces albus J1074. Microb Biotechnol. 2014;7:242–56.

    Article  CAS  Google Scholar 

  19. Huang J, Shi J, Molle V, Sohlberg B, Weaver D, Bibb MJ, et al. Cross-regulation among disparate antibiotic biosynthetic pathways of Streptomyces coelicolor. Mol Microbiol. 2005;58:1276–87.

    Article  CAS  Google Scholar 

  20. Schoenian I, Paetz C, Dickschat JS, Aigle B, Leblond P, Spiteller D. An unprecedented 1,2-shift in the biosynthesis of the 3-aminosalicylate moiety of antimycins. ChemBioChem. 2012;13:769–73.

    Article  CAS  Google Scholar 

  21. Yan Y, Chen J, Zhang L, Zheng Q, Han Y, Zhang H, et al. Multiplexing of combinatorial chemistry in antimycin biosynthesis: expansion of molecular diversity and utility. Angew Chem Int Ed. 2013;52:12308–12.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work is financially supported in part by the National Natural Science Foundation of China (31820103003, 31700042, 41676165), Guangdong Province (GDME-2018C005, 2015A030308013), and Chinese Academy of Sciences (QYZDJ-SSW-DQC004). We are grateful to Z. Xiao, A. Sun, C. Li, and Y. Zhang in the analytical facilities of SCSIO.

Author information

Authors and Affiliations

  1. CAS Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, RNAM Center for Marine Microbiology, Institutions of South China Sea Ecology and Environmental Engineering, South China Sea Institute of Oceanology, Chinese Academy of Sciences, 164 West Xingang Road, 510301, Guangzhou, China

    Chunshuai Huang, Chunfang Yang, Wenjun Zhang, Yiguang Zhu, Liang Ma, Zhuangjie Fang & Changsheng Zhang

  2. University of Chinese Academy of Sciences, 19 Yuquan Road, 100049, Beijing, China

    Chunshuai Huang, Zhuangjie Fang & Changsheng Zhang

Authors
  1. Chunshuai Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chunfang Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Wenjun Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yiguang Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Liang Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Zhuangjie Fang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Changsheng Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Changsheng Zhang.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Huang, C., Yang, C., Zhang, W. et al. Albumycin, a new isoindolequinone from Streptomyces albus J1074 harboring the fluostatin biosynthetic gene cluster. J Antibiot 72, 311–315 (2019). https://doi.org/10.1038/s41429-019-0161-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41429-019-0161-4

Search

Advanced search

Quick links