ACTINOMYCETOLOGICA
Vol. 7 No. 2,1993
Published by the Society for Actinomycetes, Japan
ABSTRACTS OF PAPERS
Code Number: AC94008
Size of files:
Text: 15K
No associated graphics files
CHEMISTRY AND BIOCHEMISTRY OF THE CHITINASE INHIBITORS,
ALLOSAMIDINS
S. Sakuda, A. Isogai^1, A. Suzukil^1 and Y. Yamada
Dept. Biotechnology, Faculty of Engineering, Osaka University,
Yamada-oka 2-1, Suita-shi Osaka 565 ^lDept. Agricultural Chemistry,
The University of Tokyo, Bunkyo-ku, Tokyo 113
Actinomycetologica, 7: 50-57, 1993
Work carried out on allosamidins, chitinase inhibitors
isolated from Streptomyces sp., is reviewed. Screening with
Candida albicans resulted in the identification of seven
natural compounds, with a similar pseudotrisaccharide structure,
but differing in the number of N-methyl groups, stereochemistry of
the hydroxyl group at C-3, and presence of O-methyl groups at C-6 .
Allosamidins have an ecdysis inhibitory activity on insect larvae.
In Saccharomyces cerevisiae demethylallosamidin induces the
formation of clusters of cells, demonstrating the role of yeast
chitinase in cell separation. In C. albicans abnormal cell
clusters are also observed during dimorphism. A pathway of
allosamidin biosynthesis is proposed and the potential role of
chitinase inhibitors, as insect growth regulators and fungicides,
is discussed .
R.L.
A STUDY ON ALKALOPHILIC ACTINOMYCETES IN YUNNAN
C.-L. Jiang, L.-H. Xu, Y.-R. Yang, L.-F. Wang, Z.-W. Shi and
G.-Y. Guo
Yunnan Institute of Microbiology, Yunnan University, 650091,
Kunming, Yunnan, China
Actinomycetologica, 7: 58-64,1993
Alkalophilic actinomycetes were isolated from alkaline soil
samples collected at Yunnan, China using a number of different
media adjusted to pH 10. Forty-nine isolates and 10 type strains of
the genus Streptomyces were selected for studying their
physiological, biochemical, morphological and chemotaxonomic
characteristics, and a cluster analysis based on their 82
unit characters was carried out. DNA-DNA homology among 9
strains selected from each cluster was determined. Characteristics
of the alkalophilic actinomycetes and relationship between the
alkalophilic and non-alkalophilic actinomycetes were discussed.
Authors' Abstract
INVOLVEMENT OF TWO GENES IN THE INDUCTION OF BETA-LACTAMASE IN
STREPTOMYCES CACAOI
H. Urake and H. Ogawara
Dept. Biochemistry, Meiji College of Pharmacy. 1-
35-23, Nozawa, Setagaya-ku. Tokyo 154
Cloning and sequencing of genes encoding beta-lactamase of
S. cacaoi show that the upstream sequence of the
beta-lactamase gene has enhancing effects on the beta-lactamase
production in S. lividans. Nucleotide sequencing of the
region reveals the presence of two regulatory genes, blaA
and blaB. In the presence of 7-aminocephalosporanic
acid, the S. cacaoi beta-lactamase gene is expressed
inducibly in S.lividans harbouring plasmid pMCP141
(constructed by inserting the beta-lactamase gene and the upstream
sequence with the two regulatory genes) and the production of
beta-lactamase increases up to eight times. On the other hand the
induction phenomenon is not observed in the clone harbouring
pMCP146 deleting the upstream sequence. The role of the two
regulatory genes is confirmed by work on mutants. The disruption of
blaA and/or blaB results in loss of inducibility and
the positive effect of blaA depends on the presence of the
blaB gene.
R. L.
"EUCARYOTIC SIGNAL TRANSDUCTION SYSTEMS IN THE BACTERIAL GENUS
STREPTOMYCES
S. Horinouchi
Dept. Agricultural Chemistry, The University of Tokyo, 1-1-1,
Yayoi, Bunkyo-ku, Tokyo 113
Actinomycetologica, 7: 68-87, 1993
A microbial hormone, A-factor, controls streptomycin
production, streptomycin resistance, and aerial mycelium formation
in Streptomyces griseus. A-factor exerts its regulatory role
by binding to a specific receptor protein which, in the absence of
A-factor, acts as a repressor-type regulator for these
morphological and physiological differentiation. In the signal
relay leading to streptomycin production, the A-factor signal is
transmitted from the A-factor receptor to the upstream activation
sequence of a regulatory gene, strR, in the streptomycin
biosynthetic gene cluster via an A-factor-dependent protein that
acts as a transcription factor for strR. The signal relay
leading to aerial mycelium formation includes proteins similar to
response regulators of the procaryotic two-component regulatory
systems and to a family of membrane translocators engaged in
ATP-dependent secretion mechanisms. Accumulating data show that a
large family of gamma-butyrolactones act as autoregulators in a
wide variety of Streptomyces spp.
In addition to the hormonal control by the autoregulators,
secondary metabolism and morphogenesis are controlled by signal
transduction systems via both procaryotic and eucaryotic protein
kinases. A pair of the AfsQ1 and AfsQ2 proteins constituting a
procaryotic-type histidine-aspartate phosphotransfer system
globally controls secondary metabolite formation in S.
coelicolor A3(2). Another pair of proteins, AfsK and AfsR,
which also serves as a global regulator for secondary metabolism in
S. coelicolor, constitutes an eucaryotic-type
phosphotransfer system in which a protein serine/threonine/
tyrosine kinase AfsK phosphorylates serine and threonine
residues of AfsR. A wide distribution of DNA sequences homologous
with the afsQI / afsQ2 and afsKl afsR genes
suggests that both procaryotic and eucaryotic protein kinases
control secondary metabolism in general in Streptomyces.
Inhibition by K-252a and staurosporine, known as eucaryotic
protein kinase inhibitors, of antibiotic production and aerial
mycelium formation of S. griseus and S. coelicolor
supports this idea.
Author's Abstract
SCREENING FOR NEW PRODUCTS OF NEW SPECIES OF DACTYLOSPORANGIUM
AND OTHER ACTINOMYCETES
T. Shomura
New Products Development, Pharmaceutical Division, Meiji Seika
Kaisha, Ltd., 2-4-16 Kyobashi, Chuo-ku, Tokyo 104
Actinomycetologica, 7: 68-87,1993
Selective methods and media for the isolation of representatives of
the genus Dactylosporangium, to be screened for new
metabolites, include pretreatment of the samples, improvement of
isolation media and optimal cultural conditions. Metabolites
produced by Dactylosporangium strains are reviewed.
R.L.
Proceedings of SAJ Symposium: New Basis for the Discovery of
Novel
Bioactive Substance
RESEARCH ON ANTIBIOTIC SCREENING IN JAPAN OVER THE LAST DECADE: A
PRODUCING
MICROORGANISM APPROACH
S. Miyadoh
Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd., Morooka,
Kohoku-ku, Yokohama
Actinomycetologica, 7: 100-106, 1993
We surveyed the research activity on antibiotic screening over the
last 10 years using data published in the Journal of Antibiotics
(1984-1993) and the Japan Kokai Patent (1983-1992) Research on new
antibiotic screening is very active in Japan, and we considered a
survey of these data to be helpful in grasping domestic and
international research trends in this field. In this report, we use
the term "antibiotics" not in the narrow sense of antimicrobial
antibiotics, but rather to mean bioactive microbial products.
Author's Abstract
SEARCH AND DISCOVERY OF SOIL MICROORGANISMS WHICH PRODUCE NEW
BIOACTIVE SUBSTANCES: SELECTIVE ISOLATION OF MICROORGANISMS AND
THEIR FERMENTATION PRODUCTS
K Suzuki
Drug Serendipity Res. Labs, Institute for Drug Discovery Res.,
Yamanouchi Pharmaceutical Co. Ltd., 1-1-8, Azusawa, Itabashi-ku,
Tokyo 174
Actinomycetologica, 7: 107-109, 1993
In Japan Saccharopolyspora strains appear to be
characteristically distributed in the subtropical regions.
Isolation of the organisms is hindered by the slow growth on
conventional actinomycete media. By using MSA-2, a medium
containing cabbage meal and sugarcane bagasse and kanamycin and
streptothricin as selective agents, producers of sporaricins and
erythromycin could be isolated. Saccharopolyspora strains
predominate in the top layer of the soil (0-5 cm depth).
R.L.
SCREENING OF BIOACTIVE SUBSTANCES OF MICROBIAL ORIGIN BASED ON
ENZYME AND RECEPTOR BINDING ASSAYS
Y. Matsuda
Tokyo Res.Labs., Kyowa Hakko Kogvo Co., Ltd.,3-6-6 Asahimachi,
Machida-shi. Tokyo 194
Actinomycetologica, 7: 110-118, 1993
ES-242-1, a novel bioxanthracene, is the first microbial compound
found to act with a novel mechanism of action on the
N-methyl-D-aspartate (NMDA) receptor and may possess
neuroprotective properties useful in the treatment of disease
involving glutamate toxicity. HS142-1 is the first compound to be
discovered as a specific antagonist for functional receptors for
natriuretic peptide; the compound would be useful to clarify the
physiological and pathophysiological functions of natriuretic
peptides. The protein kinase inhibitor K-252a was recently reported
to potentiate the activity of a neurotrophin and to promote some
neuronal survival. K-252a and its derivatives would be lead
compounds for the development of compounds therapeutically useful
in the treatment of neurological disease and injury.
Author's Abstract
SCREENING OF BIOACTIVE SUBSTANCES FROM MICROBIAL PRODUCTS USING
TISSUE AND CELL CULTURE SYSTEMS
M. Okamoto, T. Kino and M. Okuhara
Exploratory Research Laboratories, Fujisawa Pharmaceutical Co.,
Ltd., 5-2-3, Tohkoudai, Tsukuba-shi, Ibaraki 300-26, Japan
Actinomycetologica, 7: 119-127, 1993
Tissue and cell culture systems are employed for screening
bioactive substances of microbial origin. FR 900452, an antagonist
of the platelet activating factor (PAF), isolated from
Streptomyces phaeofaciens, No. 7739, is a lipophilic
compound (m.w. 411) found by screening fermentation broths for
inhibitory effects on PAF-induced platelet aggregations.
Preliminary results also suggest the use of FR for the treatment of
septic shock. By using the superfusion technique on rat aorta it is
possible to screen fermentation broths for vasodilating activity of
interest for treating ischemic heart diseases. A compound (FK 409),
isolated from S.griseosporeus, strain 16917, exhibits marked
relaxation activity, similar to that of nitroglycerine, at 0.01ug
doses. Rat spleen cells are used for screening immunosuppressants
of microbial origin, taking advantage of the blastogenetic response
of lymphocytes. FK 506, a macrolide lactone obtained from
S.tsukubaensis, shows interesting immunosuppressive effects
and is being commercialised in Japan since 1993.
R.L.
INDUSTRIAL DEVELOPMENT OF BIALAPHOS, A HERBICIDE FROM THE
METABOLITES OF
STREPTOMYCES HYGROSCOPICUS SF1293
A. Satoh, T. Murakami, H. Takebe^l, S.Imai^2 and H.
Seto^3
Pharmaceutical Technology Laboratories, Meiji Seika Kaisha, 788
Kayama, Odawara-shi, Kanagawa 250 ^1Gifu Plant, Meiji Seika Kaish
2890 Kitagata, Kitagata-cho, Motosu-gun, Gifu 501-04,
^2Pharmaceutical Research Center, Meij Seika Kaisha, 760
Morooka-cho, Kohoku-ku, Yokohama 222 ^3The University of Tokyo,
1-1-: Yayoi Bunkyo-ku, Tokyo 113
Actinomycetologica, 7: 128-132, 1993
The industrial development of the production of bialaphos, a
herbicide obtained from S.hygroscopicus, is described. The
compound is a tripeptide and represents the first herbicide of
microbial origin. The biosynthetic pathway is illustrated as well
as fermentation improvements which have increase productivity
several thousand times..
R.L.
GENETIC ASPECTS OF THE SELECTIVE PRODUCTION OF USEFUL COMPONENTS IN
THE AVERMECTIN PRODUCER STREPTOMYCES AVERMITILIS
H. Ikeda and S. Omura
School of Pharmaceutical Sciences, Kitasato University and The
Kitasato Institute, 5-9-1, Shirokane, Minato-ku, Tokyo 108
Actinomycetologica, 7: 133-144, 1993
Avermectins, isolated from S.auermitilis, are potent
antiparasitic compounds with a broad spectrum of activity against
nematodes and arthropods, but inactive against bacteria and
fungi,
Improvements in the production involves favouring the
biosynthesis of the most effective component and the suppression of
the accumulation of useless toxic compounds, such as oligomycin. By
genetic manipulation of antibiotic biosynthesis genes, novel
intermediates or shunt products could be obtained.
R.L.
USE OF A HETEROLOGOUS GENE FOR MOLECULAR BREEDING OF ACTINOMYCETES
PRODUCING
STRUCTURALLY RELATED ANTIBIOTICS: SELF-DEFENSE GENES OF PRODUCERS
OF FORTIMICIN-A (ASTROMICIN)-GROUP ANTIBIOTICS
T. Ohta, T. Dairi, E. Hashimoto and M.
Hasegawa
Tokyo Res.Labs, Kyowa Hakko Kogyo Co., Ltd. 3-6-6 Asahi-machi,
Machida-shi, Tokyo 194
Actinomycetologica, 7: 145-155, 1993
Self-defense genes of fortimicin (Fm)group antibiotic producers
varied between genera, and can be classified into two groups
regarding to their resistance profiles and DNA homologies. DNA
sequence analyses revealed that the resistance genes of the
Streptomyces and Saccharopolyspora producers encode
methyltransferases capable of modifying 16S rRNA as same as kamB
of a nebramycin producer, S.tenebrarius, and that those
of the Micromonospora and Dactylosporangium producers
encode another type of 16S rRNA methyltransferases similar to
grmA of a gentamicin producer, M.purpurea. A Fm-A
producer, M. olivasterospora, transformed by the
Fm-resistance gene (fmrT) of S. tenjimariensis showed
significant increase of the resistance level to Fm-A. This result
indicated that heterologous genes from producers of the
structurally related antibiotics are useful as DNA sources for the
molecular breeding of antibiotic producers.
Authors' Abstract
Copyright 1994 C. E. T. A.
