Anti-infectives (TracK)
Selective Anti-mycobacterial Activity of Fungal Calpinactam, New Aminocaprolactam Peptide
Nobuhiro Koyama Graduate School of Pharmaceutical Sciences
Kitasato University
Abstract:
Our research group has focused on discovery of new anti-mycobacterial agents that selectively inhibit the growth of Mycobacterium smegmatis. In the course of this screening, a fungal strain Mortierella alpina FKI-4905 was selected as a potential candidate from 30,000 microbial culture broths. A new compound named calpinactam (13.0 mg) was isolated from the culture broth (1.0 L) of this strain by solvent extraction, ODS column chromatography and preparative HPLC. From the various spectral analyses, the compound was elucidated to be a hexapeptide having an aminocaprolactam ring at its C terminal, which was seen in the structures of siderophore mycobactins. Its absolute stereochemistry was determined by chiral amino acid analysis.
In contrast to mycobactins, calpinactam didn’t form iron complex. With a paper disk method, calpinactam was selectively active against M. smegmatis among various microorganisms including gram-positive and gram-negative bacteria, fungi and yeasts. With a liquid microdilution method, calpinactam inhibited the growth of M. smegmatis, M. bovis, and M. tuberculosis with MIC values of 0.78, 3.13 and 12.5 µg/ml, respectively. Furthermore, calpinactam was found to inhibit both fatty acid and mycolic acid synthesis in M. smegmatis. Calpinactam might act on biosynthetic pathway of cell wall in mycobacteria, leading to selective anti-mycobacterial activity.
