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 lg ml À1 , respectively. The Journal of Antibiotics (2010) 63, 183-186; doi:10.1038/ja.2010.14; published online 26 February 2010Keywords: anti-mycobacterial peptide; calpinactam; fungal metabolite; mycobactin; tuberculosis INTRODUCTIONOur research group has focused on the discovery of anti-infectives from microbial metabolites. 1-5 Tuberculosis (TB) is still the greatest single infectious cause of mortality in the world, together with human immunodeficiency virus and malaria. 6 Moreover, the spread of human immunodeficiency virus has resulted in an increase in the number of TB patients. 7 However, no new anti-TB agents have been developed for over 30 years, and only five anti-TB drugs can be used clinically at present. It is therefore increasingly urgent and necessary to discover anti-TB drugs with a new mechanism of action. As isoniazid and ethambutol, first-line anti-TB drugs, show selective inhibition against Mycobacteria, we have screened for microbial metabolites having selective inhibition against Mycobacterium smegmatis among 14 test microorganisms, including Gram-positive and Gram-negative bacteria, fungi and yeasts. By this screening system, we discovered and reported lariaitins, new lasso polypeptides, from actinomycete Rhodococcus metabolites. [8][9][10] During the continuous screening program, we isolated calpinactam (Figure 1), a new hexapeptide with a caprolactam ring at the C-terminal, from the culture broth of the fungal strain Mortierela alpina FKI-4905 (Figure 2). The structure elucidation of calpinactam is described in detail elsewhere. 11 In this report, the taxonomy of the producing strain, fermentation, isolation and biological properties of calpinactam are described.
A new fungal metabolite designated calpinactam (1) was isolated from the culture broth of Mortierella alpina FKI-4905, and its structure was elucidated by spectroscopic analyses including NMR experiments. Calpinactam was found to be a hexapeptide with a caprolactam ring at its C-terminal. Its absolute stereochemistry was determined by amino acid analysis and total synthesis. Calpinactam selectively inhibited the growth of mycobacteria among various microorganisms. The MIC values of calpinactam against Mycobacterium smegmatis and M. tuberculosis were 0.78 and 12.5 microg/mL, respectively.
Calpinactam (I), a new antimycobacterial agent, is isolated from the culture broth of the fungal strain Mortierella alpina FKI‐4905.
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