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ACTINOMYCETOLOGICA Vol. 8, No. 2, 1994 Published by the Society for Actinomycetes, Japan
ABSTRACTS OF PAPERS
Code Number: AC95010
Sizes of Files:
Text: 29K
No associated graphics
Studies on the Biosynthesis of FosfomycinT.Hidaka, T.Kuzuyama and H.Seto Inst. Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113, Japan Actinomycetologica, 8: 41-46, 1994 The biosynthetic pathway of fosfomycin (FM) and cloning the biosynthesis genes in S.wedmorensis 144-91 are reported. FM has almost no toxicity towards man, exhibits a broad antibacterial spectrum covering many pathogenic and opportunistic Gram-positive and Gram-negative bacteria and it is widely used in therapy. The antibiotic has a stable epoxide and a direct carbon-phosphorus (C-P) bond, both of which are essential for its antimicrobial activity. The first biosynthetic reaction, the C-P bond formation, is catalyzed by PEP phosphomutase. The successive steps are decarboxylation of PnPy, methylation of PnAA and epoxide formation (dehydrogenation of HPP). The FM biosynthetic gene cluster of S.wedmorensis was identified. R.L.
Taxonomic Status of Streptomyces coelicolor A3(2) and Streptomyces lividans 66
K.Hatano, T.Tamura and T.Nishii
Inst. Fermentation, 2-17-85 Juso-honmachi, Yodogawa-ku, Osaka 532, Japan Actinomycetologica, 8: 47-50, 1994 Morphological and cultural characteristics, and DNA-DNA relatedness of Streptomyces coelicolor A3(2) and S.lividans 66 were examined and compared with those of S.coelicolor Mller, S.lividans ISP5434 and S.violaceoruber ISP 5049 in order to clarify taxonomic status of the species. S.coelicolor A3(2) is distinctly different from the type strain S. coelicolor Mller, but closely related to S.violaceoruber ISP5049. In addition, S.lividans 66 closely resembles S.lividans ISP5434 and S.violaceoruber ISP5049. Abridged Authors' Abstract
Antimicrobial Activity of Electrolyzed NaCl Solutions: Effect on the Growth of Streptomyces spp. K.Hotta^1, K.Kawaguchi^1, F.Saitoh^1, N.Saito^2, K.Suzuki^2, K.Ochi^3 and T.Nakayama^4 Depts Bioactive Molecules^1 and Pathology^2, Nat. Inst. Health, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162, ^3Natl. Food Res. Inst., 2-1-2 Kannondai, Tsukuba 305 and ^4Artec, 1-17-7 Hyakunincho, Shinjuku-ku, Tokyo 169, Japan.
Actinomycetologica, 8: 51-56, 1994 An acidic solution (pH 2.5~2.6) with a high oxidation - reduction potential (ORP; about +1,170 mV) and an alkaline one (pH 11.5~11.7) with a low ORP (about -880mV) that resulted from electrolysis of 20 mM NaCl (dissolved in water) were tested for their effect on the growth of Streptomyces spp. When spores were exposed to the electrolyzed solutions for 1 minute, colony formation was completely inhibited by the acidic solution, but only slightly by the alkaline one. Extending the exposure time (10 minutes) resulted in marked inhibition. One minute exposure to a mixture of the solutions, showed strong inhibition, weaker however than that of the acidic one. When unexposed spores were streaked and incubated on ISP No. 4 medium plate with a gradient of the two solutions, growth inhibition towards the acidic solution side was observed, although the pH of the acidic solution end of the plate was around 6.2. Thus it seems unlikely that pH contributed to antimicrobial activity. Clear growth inhibition by the acidic solution was observed without direct contact with spores, probably because of chlorine gas release. Acidic solutions (pH 2.6~2.7) resulting from the electrolysis of 20 mM of Na2SO4 show no significant antimicrobial activity when tested by the gradient plate method. Therefore it appears that chlorine plays a key role in the antimicrobial activity of the acidic electrolyzed NaCl solution. Abridged Authors' Abstract
Isolation of Actinomycetes from Pine Litter Layers S.Matsukuma, T.Okuda and J.Watanabe
Dept. Microbiology and Taxonomy, Nippon Roche Res. Center, 200, Kajiwara, Kamakura, Kanagawa 247, Japan Actinomycetologica, 8: 57-65, 1994 Methods for the selective isolation of actinomycetes from pine litter layers were evaluated. Pretreatment of sampled material with sodium dodecyl sulfate and addition of nalidixic acid to the agar media reduced bacterial growth. The addition of benlate to the agar medium was effective in reducing fungal growth. By removing actinomycetes from the surface of pine needles with 70% of ethanol and sodium hypochlorite, it was possible to isolate actinomycetes present under the waxy layer of needles. Comparative studies of isolates obtained from pine litter layers showed qualitative and quantitative differences according to layer location. Abridged Authors' Abstract
Cloning and sequencing of a phnO-like gene from Streptomyces griseus B2682 R.Ohtaki, H.Urabe and H.Ogawara
Dept. Biochemistry, Meiji College of Pharmacy, Nozawa-1, Setagaya-ku, Tokyo 154, Japan
Actinomycetologica, 8: 66-68, 1994 Two synthetic oligodeoxyribonucleotides were used as PCR primers: 5'-CACGGATCCAAGATCGCCGACTTCGGCCTGGCCCGC and 5 -ACGAATTCACGCCGAAGGCCCACACGTCCGA. Nucleotide sequences were deduced from those in the Escherichia coli phnO gene. PCR was carried out using chromosomal DNA of S.griseus B2682 as template. The 200-bp PCR product was used as a probe. Following digestion with SalI and Southern hybridization, a 4.4-kb fragment was ligated with pUC 118, and E. coli JM109 was transformed with the plasmid. Three strong positive clones were obtained among about 1500 transformants. Plasmids isolated from the clones showed identical restriction enzyme patterns. Analysis of the nucleotide sequence of the fragment showed that the phnO gene encodes a protein consisting of 150 amino acids. The phnO-like gene may be of use for cloning genes implicated in the synthesis of C-P compounds by Streptomyces. R.L.
Isolation and Characterization of Temperate Phage SAt28 and Its Deletion Mutants Infecting Streptomyces azureus ATCC 14921 H.Suenaga^1, M.Rodprapakorn, K.Hitomi^2 and S.Ogata
Microbial Genetics Div., Inst. Genetic Resources, Fac. Agriculture, Kyushu Univ., Fukuoka 812, ^1Fukuoka Ind.Res.Inst., 332-1, Kamikoga, Chikushino-shi, Fukuoka 818, ^2Shiraoi Factory, Asahi Chem. Ind. Co., Ltd., Shiraoi-cho, Shiraoi-gun, Hokkaido 059-09, Japan Actinomycetologica, 8: 69-72, 1994 Characteristics of a temperate phage SAt28, showing a broad host range, isolation of deletion mutants and restriction enzyme analysis of DNA are reported. Phage SAt28, belonging to Siphoviridae, has a hexagonal head of 60nm in diameter, a flexible tail 190nm long and 8nm wide. The host range was examined on 50 strains of Streptomyces species. The phage formed turbid plaques on S.azureus ATCC 14921 and clear ones on other 11 strains. Two types of deletion mutants, a turbid plaque forming-derivative (SAt28 DP1) and a clear plaque forming-derivative (SAt28DP2) were obtained by using S.azureus as host. From the results it appears that in phage SAt28 DNA a non-essential region for growth is located near the HindIII-3 site. It is assumed that 2 kb and 4 kb of a foreign DNA fragment could be introduced into the DNAs of the wild-type and of the deletion mutant respectively. R.L. Identification of Strain MH193-16F4, a Benanomicin Producing Actinomycete, to Actinomadura spadix N.Kinoshita, M.Okada and M.Hamada
Inst. Microbial Chemistry, 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo 141, Japan Actinomycetologica, 8: 73-78, 1994 Taxonomic characteristics of actinomycete strain MH193-16F4, isolated from a soil sample and producing the new antifungal and antiviral antibiotics benanomicins A and B are reported. The antibiotics show good activity against a wide range of fungi in vitro and in vivo and also against de novo infection of human T-cells with human immunodeficiency virus type 1 (HIV 1). Strain MH193-16F4 appears closely related to Actinomadura spadix. R.L.
Characterization of Various Streptomyces griseus Strains as to Aerial Mycelium- and Submerged Spore-Formation K.Ochi, Y.Inatsu, S.Okamoto, A.Penyige, T.Kudo^1 and K.Hotta^2
Nat. Food Res. Inst., 2-1-2 Kannondai, Tsukuba, Ibaraki 305, ^1Japan Collection of Microorganisms, Inst.Physical and Chemical Res. (RIKEN), 2-1 Hirosawa, Wako, Saitama 350-01 and ^2Nat. Inst. Health, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162, Japan
Actinomycetologica, 8: 79-84, 1994 Several strains of S.griseus were investigated as to their ability to form submerged aerial mycelium and spores in liquid media. Only a limited number of strains showed this ability and only in specific media. The effect of decoyinine, a specific inhibitor of GMP synthetase, on the induction of aerial mycelium formation was investigated in an aerial mycelium-suppressive medium. A majority of S.griseus strains (14 on 23) developed aerial mycelium. Results show that the sporulation in liquid culture involves procedures different from those involved in aerial mycelium formation and sporulation on agar plates. Analysis of ribosomal AT-L30 proteins was used for the classification of the strains. R.L.
Abstracts of Symposia
SAJ Symposium '94 - I New Impact in Streptomyces Genetics
Held on June 23,1994 in Hiroshima and organized by H.Kinashi and O.Nimi (Hiroshima University)
Introductory Remarks H.Kinashi
Dept. Fermentation Technology, Faculty of Engineering, Hiroshima University Actinomycetologica, 8: 86, 1994 The history of research on actinomycete plasmids is summarised. The idea that bacteria have a circular chromosome and that linear chromosomes are monopoly of eukaryotes appears no longer valid. With reference to actinomycetes, the first linear plasmid pSLA2 was found in 1979 in Streptomyces rochei. Then, several "giant" linear plasmids represented by SCP1 were isolated and finally the S.lividans 66 chromosome was proved to posses a linear topology. The nature of genetic instability in Streptomyces could not be understood until the linearity of the Streptomyces chromosomes was discovered. Knowledge and tools necessary to solve interesting problems in streptomyceces are now available. Namely: what triggers genetic instability, what is the replication mechanism of linear chromosomes, what is the evolutional relationship between linear and circular chromosomes, how linear plasmids interact with chromosomes and what is the molecular reason of uni- and bi-directional gene transfer during conjugation. Abridged Authors' Abstract
Linear Plasmids from Actinomycetes
H.Kinashi Dept.Fermentation Technology, Fac.Engineering, Hiroshima Univ., 1-4-1 Kagamiyama, Higashihiroshima-shi, Hiroshima 724, Japan Actinomycetologica, 8: 87-96, 1994 Linear plasmids in actinomycetes appear to be formed by deleting the central large part of the chromosome and retaining the terminal inverted repeats. Data so far accumulated on linear plasmids are reported and their origin, terminal structure, replication, maintenance and function, with particular reference to SCP1 and pSLA2, are discussed. SLP2, pHG, pBL1, pSCL and other linear plasmids in b-lactam producers and plasmids in S.rimosus are also reviewed. R.L. Structural instability of the Streptomyces lividans 66 Chromosome and Related Effects M.Redenbach^1, A.Arnold^2, U.Rauland^2 and J.Cullum^2 ^1Hiroshima Univ., Fac. Engineering, Higashi Hiroshima 724, Japan and ^2LB Genetik, Universit„t Kaiserslautern, 67663 Kaiserslautern, Gerrnany Actinomycetologica, 8: 97-102, 1994 The so-called genetic instability of S.lividans is due to complex genomic rearrangements such as large deletions which in most cases are accompanied by amplifications of certain chromosomal segments adjacent to the deletion ends. S.lividans 66 possesses at least two unstable chromosomal markers: the chloramphenicol resistance and the arginine biosynthesis ones. By analyzing an ordered cosmid library of the "unstable region", the authors conclude that deletions happen from both ends of the linear chromosome. A model leading to amplification and circularization is proposed. R.L.
The Linear Chromosomes of Streptomyces: Structure and Dynamics
C.W.Chen, Y.-S.Lin, Y.-L.Yang, M.-F.Tsou, H.-M.Chang, H.M.Kieser^1 and D.A.Hopwood^1 Inst. Genetics, National Yang-Ming Univ., Shih-Pai, Taipei 112, Taiwan and ^1John Innes Centre, Norwich Research Park, Norwich, UK Actinomycetologica, 8: 103-112, 1994 The linearity of the chromosome has been observed in several Streptomyces species. The termini of the chromosomes contain inverted repeats, and carry covalently-bound proteins at the 5' end, presumably the primer for replication. The terminal sequence exhibits abundant palindromes, resembling those of several linear Streptomyces plasmids for the first 12~17 bp. In spite of this, the terminal DNA sequences among different species are not highly conserved over long distances. A functional oriC has been located at the center of the chromosomes of S. coelicolor and S.lividans. These chromosomes appear to replicate bi-directionally from the center and are presumably patched up at the ends by protein-primed replication. At least in S.lividans, the telomeres are dispensable and the chromosome could be circularized in viable cells by targeted recombination, which removed the telomeres and joined the two arms. The circularized chromosomes were unstable, undergoing further rearrangements, and resulted in relatively poor growth and sporulation. Long stretches of DNA on various Streptomyces chromosomes are prone to spontaneous deletions and amplifications. In S.lividans and S.coelicolor, the unstable regions correspond to the termini. Moreover, circularized chromosomes, containing deletions of several hundreds of kb in the terminal regions, were found in some spontaneous deletion mutants. These observations indicate the readiness of the linear chromosome to be circularized and implicate the termini in the structural instability of Streptomyces chromosomes. Abridged Authors' Abstract
SAJ Symposium '94 - II Taxonomic Status of Streptomyces Hosts for Gene Manipulation - Streptomyces coelicolor A3(2), S.kasugaensis and S.lividans -
Held on June 23, 1994 in Hiroshima and organized by K.Hotta (National Inst. of Health) and O.Nimi (Hiroshima Univ.)
General Remarks on Streptomyces Hosts
K.Hotta Nat. Inst. Health, 1-23-1, Toyama, Shinjuku-ku, Tokyo 162, Japan Actinomycetologica, 8: 114-115, 1994 Streptomyces coelicolor, S.griseus, S. kasugaensis, S.lividans and S.parvulus are approved as Streptomyces hosts in the current Japanese guideline for recombinant DNA experiments. However S.coelicolor A3(2), S.lividans and S.kasugaensis have taxonomic problems. Although S. coelicolor A3(2) is genetically the best characterized strain, it had been pointed out that its taxonomic properties are different from those of S.coelicolor Mller (the type strain), but highly similar to those of S.violaceoruber Waksman and Curtis. On the other hand, the names of S.lividans and S.kasugaensis have no taxonomic legitimacy. The aim of this Symposium is to clarify their taxonomic status as well as to establish a consensus for a practical use of their nomenclature. Abridged Author's Abstract
Taxonomic status of Streptomyces coelicolor A3(2) and Streptomyces lividans
K.Hatano Inst. Fermentation, Osaka; 2-17-85 Juso-honmachi, Yodogawa-ku, Osaka 532, Japan Actinomycetologica, 8: 115, 1994 Streptomyces coelicolor A3(2) and S.lividans 66 were examined for their morphological and cultural characteristics as well as DNA-DNA relatedness in comparison with those of S.coelicolor Mller, S.lividans ISP5434 and S.violaceoruber ISP5049 in order to clarify their taxonomic status. S.coelicolor A3(2) is distinctly different from the type strain, but closely related to S.violaceoruber ISP 5049. On the other hand, S.lividans 66 was found to have taxonomic characteristics that closely resemble those of S.lividans ISP5434 and S.violaceoruber ISP5049. These results indicate that S.coelicolor A3(2), S.lividans 66 and S.lividans ISP5434 are closely related to S.violaceoruber. Abridged Author's Abstract
Taxonomic Status of Streptomyces kasugaensis
M.Hamada Inst. Microbial Chemistry, 3-14-23, Kamiosaki, Shinagawa-ku, Tokyo 141, Japan Actinomycetologica, 8: 116, 1994 In order to establish the taxonomic status of S.kasugaensis, morphology, physiology, cell wall type and DNA of two strains, M338-M1 and MB273-C4, were investigated. Both strains show spiral aerial mycelium which at maturity forms chains of 10~50 spores with smooth surface. Aerial mass color is grey. The cell wall contains LL-2,6-diaminopimelic acid. A data base search showed similarity of the strains with S.xantholiticus. Direct comparison with strain IMC S-0620 (=ISP5244) of the latter species allowed the two species to be distinguished. DNA homology was high (77% or higher) between the two S.kasugaensis strains, and low (21% or lower) between S.kasugaensis and S.xantholiticus. Clear differences were also observed in the RAPD profiles.
Streptomyces kasugaensis is thus proposed as an independent and new species. Abridged Author's Abstract
SFBJ-SAJ Joint Symposium: New Targets in Actinomycetes Held on July 5, 1994 in Tokyo and organized by M.Shoda (Tokyo Inst. of Technology), H.Osada (Inst. of Physical and Chemical Research), T.Manome (Sankyo) and K.Hotta (Natl. Inst. of Health)
Introductory Remarks K.Hotta Dept. Bioactive Molecules, Nat. Inst. Health, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162, Japan Actinomycetologica, 8: 118, 1994 The aim of the first joint symposium with the Society for Fermentation and Bioengineering, Japan (SFBJ) is to discuss actinomycetes as producers of biologically active substances. Antibiotics have been and still are playing the important role as chemotherapeutic agents. Recently, non-antibiotic bioactive substances and non-antibiotic activities of antibiotics have been explored, not only as therapeutic agents, but also as low molecular probes for analyzing cell functions. Approaches to the search for new bioactive substances are based on the screening of naturally occurring microorganisms and on biotechnological manipulation of known producers. The importance of establishing reliable assay systems, isolation methods, genetic manipulations for the production of target compounds is stressed. Abridged Author s Abstract
Antioxidative Agents of Microbial Origin
H.Seto Inst. Molecular and Cellular Biosciences, Univ. Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113, Japan Actinomycetologica, 8: 119, 1994 Free radicals including active oxygens are highly reactive, attacking cellular membrane, proteins and genes and resulting in several diseases (atherosclerosis, inflammation, ischemia-reperfusion injury, etc.). In addition, senility and cancer initiation are also believed to involve active oxygen species. Antioxidants of microbial origin were screened using rat liver microsomes as an assay system. New metabolites, benthocyanins A, B and C, and benthophoenin were isolated from Streptomyces prunicolor and antiostatins from S.cianeus. Antiostatins are the first carbazole derivatives that possess an acetamide group or a substituted urea residue in addition to a long alkyl chain and show interesting activities in vivo and ex vivo experiments. Carquinostatin A, isolated from S.exfoliatus by screening with neuronal hybridoma N18-RE-105 cells, shows brain protecting activity in ischemia-reperfusion injury Abridged Author's Abstract
Screening of Bioactive Microbial Products (Molecular Probes) which Regulate Mammalian Cell Functions H.Osada
Inst. Physical and Chemical Res., 2-1 Hirosawa, Wako 351-01, Japan Actinomycetologica, 8: 120-121, 1994
The results of a search for microbial inhibitors regulating mammalian cell function are reported. As a screening system the bleb forming assay, using human leukemia K-562 cells, was employed. In the test, tumor promoting phorbol esters (PDBu) induce morphological changes of the cell surface, caused by the activation of protein kinases or the inactivation of protein phosphatases. During the screening, new indolocarbazole compounds, RK-286C and RK-1409, structurally related to staurosporine, were isolated as inhibitors of bleb-formation. Tautomycin was isolated as an antifungal antibiotic as well as an inducer of the blebs. Because protein phosphorylation and dephosphorylation is recognized as very important in the regulation of the mammalian cell function, the inhibitors are regarded as potential tools for studying the molecular basis of mammalian cell proliferation and differentiation. Abridged Author's Abstract
Search for Actinomycetes in Screening for New Bioactive Compounds
K.Suzuki, K.Nagai, Y.Shimizu and Y.Suzuki
Drug Serendipity Res. Labs., Inst. Drug Discovery Res., Yamanouchi Pharm. Co., Ltd., 1-1-8 Azusawa, Itabashi-ku, Tokyo 174, Japan Actinomycetologica, 8: 122-127, 1994 Results of selective isolation of rare actinomycetes as the emerging target source of both antibiotic and non-antibiotic bioactive substances are reported. Further developments in the methods for selective isolation of actinomycetes in combination with ecological studies will be useful in deciding new strategies in the discovery of more attractive producers of bioactive compounds. R.L.
Butyrolactone Auto-regulators of Streptomyces Y.Yamada, T.Nihira and S.Sakuda Dept. Biotechnology, Fac. Engineering, Osaka Univ., 2-1 Yamada-oka, Suita-shi, Osaka 565, Japan Actinomycetologica, 8: 128-129, 1994 Endogenous butyrolactones as Streptomyces autoregulators (cytodifferentiation or secondary metabolite production) are reviewed. The biosynthesis of VB A (virginiae butanolide A, isolated from S.virginiae) has been determined and purification and structure of VB receptor protein are reported. R.L.
Latent Functions in Actinomycetes and Manipulation for Their Expression
K.Hotta, J.Ishikawa, F.Yamashita^1, S.Takamura^1, Y.Hosoya^1 and Y.Okami^1 Nat. Inst. Health, 1-23-1, Toyama, Shinjuku-ku, Tokyo 162 and ^13-14-23, Kamiosaki, Shinagawaku, Tokyo 141, Japan. Actinomycetologica, 8: 130-131, 1994 Protoplast fusion was attempted between streptomycin (SM)-producing S. griseus and istamycin producing S.tenjimariensis. One of the strains produced a novel antibiotic named indolyzomycin. Induction or stimulation of antibiotic production in actinomycetes by kanamycin (2 strains), tetracycline (8), chloramphenicol (1), ampicillin (6) and nalidixic acid (1) was observed. In non-antibiotic producers incubation with amino acid analogues (fluorophenylalanine, canavanin and a-aminoethylcystein) induced antibiotic production (10% of the strains). Actinomycete strains, incubated in a nutritionally rich medium, were washed and transferred to a synthetic medium containing a specific amino acid as sole carbon and nitrogen sources. A strain of S.chattanoogensis yielded fredericamycin, whereas it produced only polyene antibiotics in the nutritionally rich medium. The results described above indicate that there are cryptic or latent functions whose expression is suppressed under usual conditions. R.L.
Selective Production of Maridomycin III and Its Scale Up in Maridomycin Fermentation E.Higashide Fac. Agriculture, Okayama Univ., 1-1-1 Tsushimanaka, Okayama 700, Japan Actinomycetologica, 8: 132-133, 1994 Addition of several amino acids (homoserine, threonine, methionine and isoleucine) and fatty acids (a-amino butyric acid and a-keto butyric acid), resulted in an increase of maridomycin III (ML-III) production by Streptomyces hygroscopicus B-50501). S.hygroscopicus No. B-5050 HA appeared most sensitive to valine followed by serine, homoserine, a-amino butyric acid and leucine. A valine resistant capable of accumulating propionyl CoA was characterized by preferential production of ML-III. The influence of fermentation parameters on production and recovery was also established. R.L.
Biosynthesis of the Pradimicin and Benanomicin Family of Antibiotics by Actinomadura S.Kakinuma^1, T.Furumai^2 and T.Oki^3 1Dept Immunology, Center for Basic Res., Kitasato Inst., 5-9-1 Shirokane, Tokyo 108, ^2Bristol-Myers Squibb Pharm. Res. Inst., 5 Research Parkway, P.O. Box 5100, Wallingford, U.S.A., ^3Biotechnol.Res.Center, Toyama Prefectural Un., 5189 Kosugi-machi, Toyama 939-03, Japan. Actinomycetologica, 8: 134-138, 1994 The biosynthetic pathways of pradimicins produced by Actinomadura verrucosospora subsp. neohibisca E-40) and of benaniomicins (Actinomadura sp., AB 1236) are illustrated. R.L.
Manufacturing of the Acylated Macrolide Antibiotic AIV by Bioconversion Method and Construction of a Genetically-Engineered Strain for Direct Fermentative Production of AIV A.Arisawa, H.Tsunekawa, K.Okamura^1, R.Okamoto and M.Okabe^2 Process Development Labs., ^1Central Res. Labs, Mercian Co., 4-9-1 Johnan, Fujisawa-shi, Kanagawa 251, ^2Fac. Agriculture, Shizuoka Univ., 836 Ohya, Shizuoka-shi, Shizuoka 422, Japan Actinomycetologica, 8: 139, 1994 AIV (3-O-acetyl 4"-O-isovaleryltylosin) is an industrially important macrolide antibiotic, used in veterinary medicine and known to inhibit the growth of tylosin-resistant bacteria. AIV is produced by bioconversion of tylosin, produced by Streptomyces fradiae, using S.thermotolerans as a converter. The report deals with the isolation, by NTG mutagenesis, of a strain of S.thermotolerans with high conversion activity but lacking carbomycin production. A genetically-engineered strain, producing AIV in the single step fermentation, was obtained. R.L. Copyright 1995 CETA
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