Abstract
Calpinactam, a new anti-mycobacterial agent, was isolated from the culture broth of a fungal strain Mortierella alpina FKI-4905 by solvent extraction, octadecyl silane column chromatography and preparative HPLC. Calpinactam was active only against Mycobacteria among various microorganisms, including Gram-positive and Gram-negative bacteria, fungi and yeasts. Calpinactam inhibited the growth of Mycobacterium smegmatis and Mycobacterium tuberculosis with MIC values of 0.78 and 12.5 μg ml−1, respectively.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Fukumoto, A. et al. Cyslabdan, a new potentiator of imipenem activity against methicillin-resistant Staphylococcus aureus, produced by Streptomyces sp. K04-0144. I. Taxonomy, fermentation, isolation and structural elucidation. J. Antibiot. 61, 1–6 (2008).
Fukumoto, A. et al. Cyslabdan, a new potentiator of imipenem activity against methicillin-resistant Staphylococcus aureus, produced by Streptomyces sp. K04-0144. II. Biological activities. J. Antibiot. 61, 7–10 (2008).
Iwatsuki, M. et al. Guadinomines, Type III secretion system inhibitors, produced by Streptomyces sp. K01-0509. I: taxonomy, fermentation, isolation and biological properties. J. Antibiot. 61, 222–229 (2008).
Iwatsuki, M. et al. Guadinomines, Type III secretion system inhibitors, produced by Streptomyces sp. K01-0509. II: physico-chemical properties and structure elucidation. J. Antibiot. 61, 230–236 (2008).
Fukuda, T., Hasegawa, Y., Sakabe, Y., Tomoda, H. & Omura, S. Citrinamides, new potentiators of antifungal miconazole activity, produced by Penicillium sp. FKI-1938. J. Antibiot. 61, 550–555 (2008).
NIAID's Tuberculosis Antimicrobial Acquisition & Coordinating Facility (TAACF). http://www.Taacf.org/about-TB-background.htm (accessed 18 January 2010).
O’Brien, R. J. Global alliance for TB drug development. Scientific blueprint for TB drug development. Tuberculosis 81, 1–52 (2001).
Iwatsuki, M. et al. Lariatins, antimycobacterial peptides produced by Rhodococcus sp. K01-B-0171, have alasso structure. J. Am. Chem. Soc. 128, 7486–7491 (2006).
Iwatsuki, M. et al. Lariatins, novel anti-mycobacterial peptides with a lasso structure, produced by Rhodococcus jostii K01-B0171. J. Antibiot. 60, 357–363 (2007).
Iwatsuki, M. et al. Lys17 in the ‘lasso’ peptide lariatin A is responsible for anti-mycobacterial activity. Bioorg. Med. Chem. Lett. 19, 2888–2890 (2009).
Koyama, N. et al. Structure and total synthesis of fungal calpinactam, a new anti-mycobacterial agent. Org. Lett. 12, 432–435 (2010).
Altschul, S. F., Gish, W., Miller, W., Myers, E.W & Lipman, D. J. Basic local alignment search tool. J. Mol. Biol. 215, 403–410 (1990).
Cole, S.T. et al. Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature 6685, 515–516 (1998).
Siayden, R. A., Lee, R. E. & Barry, C. E. III Isoniazid affects multiple components of the type II fatty acid synthase system of Mycobacterium tuberculosis. Mol. Microbiol. 38, 514–525 (2000).
Takayama, K. & Datte, A. K. Structure-to-function relationship of mycobacterial cell envelope components. Res. Microbiol. 142, 443–448 (1991).
Oishi, H. et al. Thiolactomycin, a new antibiotic. I. Taxonomy of the producing organism, fermentation and biological properties. J. Antibiot. 35, 391–395 (1982).
Sasaki, H. et al. Thiolactomycin, a new antibiotic. II. Structure elucidation. J. Antibiot. 35, 396–400 (1982).
Wang, J. et al. Platensimycin is a selective FabF inhibitor with potent antibiotic properties. Nature 7091, 358–361 (2006).
Wang, J. et al. Discovery of platencin, a dual FabF and FabH inhibitor with in vivo antibiotic properties. Proc. Natl Acad. Sci. USA 104, 7612–7616 (2007).
Vergne, A. F., Walz, A. J. & Miller, M. J. Iron chelators from mycobacteria (1954–1999) and potential therapeutic applications. Nat. Prod. Rep. 17, 99–116 (2000).
Tubaki, K. An illustrated guide to microsporic fungi (Deuteromycetes), collection, isolation and identification (in Japanese) (1998).
Jacobson, E., Granville, W. C. & Foss, C. E. Color Harmony Manual 4th edn (Container of America, Chicago, 1958).
White, T. J., Bruns, T., Lee, S. & Taylor, J. W. in PCR Protocols: A Guide to Methods and Applications (eds Innis MA, Gelfand RH, Sninsky JJ, White TJ) 315–332 (Academic Press, New York, 1990).
Acknowledgements
This study was supported by grants from Kakenhi 16073215 (to HT) and 19710191 (to NK), from the Ministry of Education, Culture, Sports, Science and Technology, Japan and the Uehara Memorial Foundation (to HT). We thank to Ms Miki Matsuba (Teshima), Microbiological Research Institute Otsuka Pharmaceutical Co, Ltd, for the measurement of MICs of mycobacteria.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Koyama, N., Kojima, S., Nonaka, K. et al. Calpinactam, a new anti-mycobacterial agent, produced by Mortierella alpina FKI-4905. J Antibiot 63, 183–186 (2010). https://doi.org/10.1038/ja.2010.14
Received:
Revised:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/ja.2010.14
Keywords
This article is cited by
-
New polycyclic tetramate macrolactams with antimycobacterial activity produced by marine-derived Streptomyces sp. KKMA-0239
The Journal of Antibiotics (2024)
-
Non-canonical two-step biosynthesis of anti-oomycete indole alkaloids in Kickxellales
Fungal Biology and Biotechnology (2023)
-
Kimidinomycin, a new antibiotic against Mycobacterium avium complex, produced by Streptomyces sp. KKTA-0263
The Journal of Antibiotics (2022)
-
Steffimycin E, a new anti-mycobacterial agent against Mycobacterium avium complex, produced by Streptomyces sp. OPMA02852
The Journal of Antibiotics (2020)
-
MS network-based screening for new antibiotics discovery
The Journal of Antibiotics (2019)
