FR901451 substance, process for preparation thereof and use ther

Details FR901451 substance, process for preparation thereof and use ther FR901451 substance, process for preparation thereof and use ther

1994-01-24

1995-04-25

Lilling, Herbert J.

Chemistry: molecular biology and microbiology

Micro-organism, tissue cell culture or enzyme using process...

Preparing heterocyclic carbon compound having only o, n, s,...

435 711, 4352521, 435822, C12P 104, C12P 2100, A61K 3574

Patent

active

054097010

DESCRIPTION:

BRIEF SUMMARY
TECHNICAL FIELD

This invention relates to a new FR901451 substance. More particularly, this invention relates to a new FR901451 substance and its pharmaceutically acceptable salts which have a human leukocyte elastase-inhibiting activity, to a process for preparation thereof, and to a pharmaceutical composition comprising the same and to a method of use thereof.


DISCLOSURE OF INVENTION

The FR901451 substance can be produced by culturing a FR901451 substance-producing strain of the genus Flexibacter in a nutrient medium.


THE MICROORGANISM

The microorganism which can be used for the production of FR901451 substance is a FR901451 substance-producing strain belonging to the genus Flexibacter, among which Flexibacter sp. No. 758 has been newly isolated from a soil sample collected at Hirono-cho, Chiba-ken, Japan.
A lyophilized sample of the newly isolated Flexibacter sp. No. 758 has been deposited with International Depository Authority under the Budapest Treaty, the Fermentation Research Institute, Agency of Industrial Science and Technology (1-3, Higashi 1 chome, Tsukuba-shi, Ibaraki-ken, 305 Japan) under the accession number of FERM BP-3420 (the deposited date: May 21, 1991).
It is to be understood that the production of the novel FR901451 substance is not limited to the use of the particular organism described herein, which is given for the illustrative purpose only. This invention also includes the use of any mutants which are capable of producing FR901451 substance including natural mutants as well as artificial mutants which can be produced from the described organism by conventional means such as irradiation of X-ray, ultra-violet radiation, treatment with N-methyl-N'-nitro-N-nitrosoguanidine, 2-aminopurine, and the like.
The Flexibacter sp. No. 758 has the following morphological, cultural, biological and physiological characteristics.
The methods described in Bergey's Manual of Systematic Bacteriology (Volume 3) were employed principally for this taxonomic study.
Morphological observation of strain No. 758 was carried out by the optical microscope with cells cultured on nutrient agar and Cytophaga agar at 30.degree. C. for 24 hours. Strain No. 758 was a gram-negative bacterium. It was slender rods or sometimes filaments, motile by gliding. It was about 0.8-1.0.times.15-18 .mu.m in size. Colonies of strain No. 758 were orange yellow, circular, convex, and entire-edged on nutrient agar. Results were shown in Table 1.
Physiological Characteristics of strain No. 758 were summarized in Table 2. The growth temperature was from 17.degree. C. to 44.degree. C. Strain No. 758 was oxidase positive, catalase positive, flexirubin reaction positive. Nitrate was reduced to nitrite is strain hydrolized gelatin, casein and esculin. Starch hydrolysis was negative. It was chitinase and cellulase negative. Decomposing ability of agar and alginat was negative. The mole percent G+C of the DNA was 49.8%. Acid formation was observed from D-glucose, D-xylose, D-galactose, sucrose, lactose and maltose. The following compounds were utilized as a sole carbon source: Namely, D-glucose, L-arabinose, D-xylose, D-fructose, D-mannose, D-galactose, sucrose, lactose and maltose. D-mannitol and sorbitol were not utilized.
According to Bergey's Manual of Systematic Bacteriology (Volume 3), strain No. 758 was considered to belong to genus Flexibacter from those characteristics described above. Then, we identified this strain as one strain of Flexibacter and named it Flexibacter sp. No. 758.


TABLE 1 ______________________________________ Morphological characteristics of strain No. 758 ______________________________________ gram stain negative color of colony orange yellow cell shape slender rods cell size 0.8-1.0 .times. 15-18 .mu.m motility gliding spore formation negative ______________________________________


TABLE 2 ______________________________________ Physiological characteristics of strain No. 758 conditions characteristics ______________________________________ growth temperature 17-44.degree

REFERENCES:
patent: 4971965 (1990-11-01), Ono et al.

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