7(B-3) 新規抗結核抗生物質lariatin類に関する研究(口頭発表の部)

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Tuberculosis (TB) is still the greatest single infectious cause of mortality in the world. Moreover, the spread of RIV promotes the increase in the number of tuberculosis patients. However, efficient anti-TB drugs with new mechanism of action have not been developed for last over thirty years; only 5 agents have been used as first-line anti-TB drugs. Isoniazid and ethambutol showing specific inhibition against mycobacterial growth are known to inhibit the cell wall biosynthesis. From the whole genome sequence of Mycobacterium tuberculosis, a number of enzymes are involved in the cell wall biosynthesis, which is a promising target for development of new anti-TB drugs. We have screened for antimycobacterial agents from microbial metabolites having a specific narrow-range spectrum against mycobacteria. As a part of this program, the culture broth of Rhodococcus sp. K01-B0171 isolated from the inside of the soil aggregates was selected (Fig. 2). As a result, unique cyclic peptides designated lariatins A and B were purified from supernatant of the 4 day-old culture broth of this strain by HP-20, ODS and LH-20 column chromatography and reversed-phase HPLC. The structures were elucidated by spectral analysis and advanced protein chemical methods. These peptides consist of 18 and 20 L-amino acid residues with an internal linkage between the α-amino group of ^1Gly and the γ-carboxyl group of ^8Glu. To our knowledge, the compound having the linkage is only reported for microcin J25, whose structure was recently revised from the head-to-tail cyclic structure. The three-dimensional structure of lariatin A is estimated 'lasso' structure from NMR data; the tail segment (W9-P18) passes through the ring segment (G1-E8). Lariatins A and B showed strong inhibition only against M. smegmatis among 14 microorganisms tested on the paper disk assay. The MIC values of lariatins A and B were 3.13 and 6.25 μg/mL for M. smegmstis Takeo, respectively. Lariatin A inhibited the growth of M. tuberculosis (Table 3).
天然有機化合物討論会の論文
2004-10-01

7(B-3) 新規抗結核抗生物質lariatin類に関する研究(口頭発表の部)

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