Skip to main content
SpringerLink
Log in

Unique butyric acid incorporation patterns for salinosporamides A and B reveal distinct biosynthetic origins

  • Biotechnological Products and Process Engineering
  • Published:
Applied Microbiology and Biotechnology Aims and scope Submit manuscript

Abstract

Feeding sodium butyrate (0.25–1 mg/ml) to cultures of Salinispora tropica NPS21184 enhanced the production of salinosporamide B (NPI-0047) by 319% while inhibiting the production of salinosporamide A (NPI-0052) by 26%. Liquid chromatography mass spectrometry analysis of the crude extract from the strain NPS21184 fed with 0.5 mg/ml sodium [U-13C4]butyrate indicated that butyrate was incorporated as a contiguous four-carbon unit into NPI-0047 but not into NPI-0052. Nuclear magnetic resonance analysis of NPI-0047 and NPI-0052 purified from the sodium [U-13C4]butyrate-supplemented culture extract confirmed this incorporation pattern. The above finding is the first direct evidence to demonstrate that the biosynthesis of NPI-0047 is different from NPI-0052, and NPI-0047 is not a precursor of NPI-0052.

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

Similar content being viewed by others

References

  • Byrnxe KM, Shafiee A, Nielsen J, Arison B, Monaghan RL, Kaplan L (1993) The biosynthesis and enzymology of an immunosuppressant, immunomycin, produced by Streptomyces hygroscopicus var. ascomyceticus. Dev Ind Microbiol 32:29–45

    Google Scholar 

  • Chauhan D, Catley L, Li G, Podar K, Hideshima T, Velankar M, Mitsiades C, Mitsiades N, Yasui H, Letai A, Ovaa H, Berkers C, Nicholson B, Chao TH, Neuteboom STC, Richardson P, Palladino MA, Anderson KC (2005) A novel orally active proteasome inhibitor induces apoptosis in multiple myeloma cells with mechanisms distinct from Bortezomib. Cancer Cell 8:407–419

    Article  CAS  Google Scholar 

  • Feling RH, Buchanan GO, Mincer TJ, Kauffman CA, Jensen PR, Fenical W (2003) Salinosporamide A: a highly cytotoxic proteasome inhibitor from a novel microbial source, a marine bacterium of the new genus Salinispora. Angew Chem Int Ed Engl 42:355–357

    Article  CAS  Google Scholar 

  • Gersch D, Bocker H, Thrum H (1977) Biosynthetic studies on the macrolide antibiotic turimycin using 14C-labeled precursors. J Antibiot 30:488–493

    Article  CAS  Google Scholar 

  • Groll M, Huber R, Potts BCM (2006) Crystal structures of salinosporamide A (NPI-0052) and B (NPI-0047) in complex with the 20S proteasome reveal important consequences of beta-lactone opening and a mechanism for irreversible binding. J Am Chem Soc 128:5136–5141

    Article  CAS  Google Scholar 

  • Jensen PR, Dwight R, Fenical W (1991) Distribution of actinomycetes in near-shore tropical marine sediments. Appl Environ Microbiol 57:1102–1108

    Article  CAS  Google Scholar 

  • Liu H, Reynolds KA (2001) Precursor supply for polyketide biosynthesis: the role of crotonyl-CoA reductase. Metab Eng 3:40–48

    Article  CAS  Google Scholar 

  • Macherla VR, Mitchell SS, Manam RR, Reed KA, Chao T, Nicholson B, Deyanat-Yazdi G, Mai B, Jensen PR, Fenical WF, Neuteboom STC, Lam KS, Palladino MA, Potts BCM (2005) Structure-activity relationship studies of NPI-0052, a novel marine derived 20S proteasome inhibitor. J Med Chem 48:3684–3687

    Article  CAS  Google Scholar 

  • Omura S, Takeshima H, Nakagawa A, Kanemoto N, Lukacs G (1976) Studies on carboxylic acid metabolism in a macrolide-producing microorganism using carbon-13 magnetic resonance. Bioorg Chem 5:451–454

    Article  CAS  Google Scholar 

  • Omura S, Takeshima H, Nakagawa A, Miyazawa J, Piriou F, Lukacs G (1977) Studies on the biosynthesis of 16-membered macrolide antibiotics using carbon-13 nuclear magnetic resonance spectroscopy. Biochemistry 16:2860–2866

    Article  CAS  Google Scholar 

  • Pospisil S, Cimburkova E, Krumphanzl V, Vanek Z (1985) Effect of precursors on biosynthesis of monensins A and B. Folia Microbiol 30:30–33

    Article  CAS  Google Scholar 

  • Reed KA, Manam RR, Mitchell SS, Xu J, Teisan S, Chao TH, Deyanat-Yazdi G, Neuteboom STC, Lam KS, Potts BCM. (2007) Salinosporamides D-J from the marine actinomycete Salinispora tropica, bromosalinosporamide, and thioester derivatives are potent inhibitors of the 20S proteasome. J Nat Prod 70:269–276

    Article  CAS  Google Scholar 

  • Rezanka T, Reichelova J, Kopecky J (1991) Isobutyrate as a precursor of n-butyrate in the biosynthesis of tylosin and fatty acids. FEMS Microbiol Lett 68:33–36

    Article  CAS  Google Scholar 

  • Sherman MM, Hutchinson CR (1987) Biosynthesis of lasalocid A: biochemical mechanism for assembly of the carbon framework. Biochemistry 26:438–445

    Article  CAS  Google Scholar 

  • Williams PG, Buchanan GO, Feling RH, Kauffman CA, Jensen PR, Fenical W (2005) New cytotoxic salinosporamides from the marine actinomycete Salinispora tropica. J Org Chem 70:6196–6203

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Nereus Pharmaceuticals, 10480 Wateridge Circle, San Diego, CA, 92121, USA

    Ginger Tsueng, Katherine A. McArthur, Barbara C. M. Potts & Kin S. Lam

Authors
  1. Ginger Tsueng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Katherine A. McArthur
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Barbara C. M. Potts
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kin S. Lam
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kin S. Lam.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tsueng, G., McArthur, K.A., Potts, B.C.M. et al. Unique butyric acid incorporation patterns for salinosporamides A and B reveal distinct biosynthetic origins. Appl Microbiol Biotechnol 75, 999–1005 (2007). https://doi.org/10.1007/s00253-007-0899-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00253-007-0899-7

Keywords

Search

Navigation