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PreprintCited by 9Microbial Natural Products and BiosynthesisIsoquinoline Alkaloid SynthesisPlant biochemistry and biosynthesis

The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

Maramycin, a cytotoxic isoquinolinequinone terpenoid produced through heterologous expression of a bifunctional indole prenyltransferase /tryptophan indole-lyase in S. albidoflavus

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Maleckis, Matiss, Wibowo, Mario, Williams, Sam E., Gotfredsen, Charlotte H., Sigrist, Renata, Souza, Luciano D.O., Cowled, Michael S., Charusanti, Pep, Gren, Tetiana, Saha, Subhasish, Moreira, José M. A., Weber, Tilmann, Ding, Ling·2024·ACS Chemical Biology
DOI 10.1101/2024.02.14.580309

Preprint — published as 10.1021/acschembio.4c00121 · Paper page

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Abstract

Isoquinolinequinones represent an important family of natural alkaloids with profound biological activities. Heterologous expression of a rare bifunctional indole prenyltransferase /tryptophan indole-lyase enzyme from Streptomyces mirabilis P8-A2 in S. albidoflavus J1074 led to the activation of a putative isoquinolinequinone biosynthetic gene cluster and production of a novel isoquinolinequinone alkaloid, named maramycin ( 1 ). The structure of maramycin was determined by analysis of spectroscopic (1D/2D NMR) and MS spectrometric data. The prevalence of this bifunctional biosynthetic enzyme was explored and found to be a recent evolutionary event with only a few representatives in Nature. Maramycin exhibited moderate cytotoxicity against human prostate cancer cell lines, LNCaP and C4-2B. The discovery of maramycin ( 1 ) enriched the chemical diversity of natural isoquinolinequinones and also provided new insights into crosstalk between the host biosynthetic genes and the heterologous biosynthetic genes in generating new chemical scaffolds.

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Research works printed but not linked: 50

  1. 10.1016/B978-0-12-800259-9.00006-8 · DOI
  2. 10.1128/JB.00204-08 · DOI
  3. 10.1038/nbt820 · DOI
  4. 10.1038/417141a · DOI
  5. 10.4014/jmb.1904.04015 · DOI
  6. 10.1016/J.SYNBIO.2018.09.001 · DOI
  7. 10.1038/ncomms3894 · DOI
  8. 10.1073/pnas.1110435108 · DOI
  9. 10.1021/ACSCHEMBIO.1C00737/SUPPL_FILE/CB1C00737_SI_001.PDF · DOI
  10. 10.3389/FMICB.2017.01284 · DOI
  11. 10.1021/NP030378L/ASSET/IMAGES/LARGE/NP030378LF1.JPEG · DOI
  12. 10.1021/NP50098A032 · DOI
  13. 10.1021/np990618q · DOI
  14. 10.1021/ja00365a048 · DOI
  15. 10.3390/MD19020090 · DOI
  16. 10.1021/NP900160G/SUPPL_FILE/NP900160G_SI_001.PDF · DOI
  17. 10.3390/MD19120715 · DOI
  18. 10.1016/J.BBRC.2020.12.093 · DOI
  19. 10.1021/jacs.7b02716 · DOI
  20. 10.1038/s41429-019-0161-4 · DOI
  21. 10.1016/J.BBRC.2020.12.093 · DOI
  22. 10.1021/ACSCHEMBIO.1C00869/ASSET/IMAGES/LARGE/CB1C00869_0011.JPEG · DOI
  23. 10.1016/j.ymben.2018.09.004 · DOI
  24. 10.1128/JB.128.2.644-650.1976 · DOI
  25. 10.3390/MOLECULES26216580 · DOI
  26. 10.1021/ACSCHEMBIO.1C00318/ASSET/IMAGES/LARGE/CB1C00318_0004.JPEG · DOI
  27. 10.1016/J.SYNBIO.2023.02.001 · DOI
  28. 10.1021/ACSCHEMBIO.3C00632 · DOI
  29. 10.1038/nchembio.2285 · DOI
  30. 10.1007/s00253-023-12397-4 · DOI
  31. 10.1021/NP900160G/SUPPL_FILE/NP900160G_SI_001.PDF · DOI
  32. 10.1093/NAR/GKAB1061 · DOI · Paper page
  33. 10.1038/s41587-023-01773-0 · DOI · Paper page
  34. 10.1038/nchembio.2285 · DOI
  35. 10.1107/S2059798318003352/LP5034SUP1.PDF · DOI
  36. 10.1093/NAR/GKAD984 · DOI
  37. 10.1021/acs.orglett.5b01203 · DOI
  38. 10.1021/acs.jnatprod.5b00276 · DOI
  39. 10.3390/MD19120715/S1 · DOI
  40. 10.1016/0378-1119(92)90603-M · DOI
  41. 10.1128/JB.181.1.204-211.1999 · DOI
  42. 10.1128/AEM.01672-20 · DOI
  43. 10.1016/0022-2836(70)90051-3 · DOI
  44. 10.1016/S0022-2836(83)80284-8 · DOI
  45. 10.1093/nar/gkad344 · DOI
  46. 10.1093/molbev/mst010 · DOI · Paper page
  47. 10.1371/journal.pone.0009490 · DOI · Paper page
  48. 10.1093/nar/gkab301 · DOI
  49. 10.1093/nar/gkad984 · DOI
  50. 10.3390/CANCERS13061290 · DOI

Metadata

Authors
Maleckis, M., Wibowo, M., Williams, S. E., Gotfredsen, C. H., Sigrist, R., Souza, L. D. O., Cowled, M. S., Charusanti, P., Gren, T., Saha, S., Moreira, J. M. A., Weber, T., & Ding, L.
Affiliations
  • Novo Nordisk Foundation (DK)
  • Technical University of Denmark (DK)
  • University of Copenhagen (DK)
Corresponding author
  • Weber, Tilmann
  • Ding, Ling
ORCID
Venue
ACS Chemical Biology
Publisher
openRxiv
Published
2024-02-14
Volume
19
Issue
6
Pages
1303-1310
ISSN
1554-8929 (ISSN-L)
DOI
10.1101/2024.02.14.580309
OpenAlex
W4396889550
Cited by
9
References
1
Citations by year
2026: 2 · 2025: 5 · 2024: 2
FWCI
2.57
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • ACS Chemical Biology (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
  • Technical University of Denmark, DTU Orbit (Technical University of Denmark, DTU) (submittedVersion)
Funders
  • Villum Fonden
  • National Research Foundation
  • Danmarks Grundforskningsfond (DNRF137)
  • Novo Nordisk (NNF16OC0021746, NNF20CC0035580)
  • Novo Nordisk Fonden (NNF16OC0021746, NNF22OC0079928, NNF20CC0035580, NNF22OC0079021)
Topics
  • Life Sciences › Immunology and Microbiology › Applied Microbiology and Biotechnology › Microbial Natural Products and Biosynthesis
  • Physical Sciences › Chemistry › Organic Chemistry › Isoquinoline Alkaloid Synthesis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Plant biochemistry and biosynthesis
Keywords
Streptomyces albidoflavus, bifunctional enzyme, heterologous expression, alkaloid biosynthesis, gene cluster activation, structure elucidation, cytotoxicity, prostate cancer, LNCaP cells
MeSH terms
Antineoplastic Agents, Dimethylallyltranstransferase, Multigene Family, Humans, Isoquinolines, Streptomyces, Terpenes, Cell Line, Tumor

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