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ACTINOMYCETOLOGICA Vol. 4 No. 2, 1990 Published by the Society for Actinomycetes, Japan
Code Number: AC91006
Sizes of Files:
Text: 10.4K
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Abstracts of papers Breeding of OA-6129 carbapenem-producing Streptomycetes and biosynthesis of carbapenems
Kojima, I. Mercian Corporation, Central Research Laboratories, 4-9-1 Johnan, Fujisawa 251, Japan Actinomycetologica, 4: 77-84, 1990 Streptomyces fulvoviridis A933 17M9 produces a range of carbapenem antibiotics such as PS-5, epithienamycins A and C, and MM17880, and the mutant 1501 derived from this strain accumulates OA-6129 carbapenems (i.e. OA6129 A, B1, B2, and C) specifically because of a defect in A933 acylase. Further mutagenesis of the mutant 1501 yielded three types of blocked mutants sequentially: OA-6129 A, Bl, and B2 producers; OA-6129 A and B2 producers; and an OA-6129 A producer. The product analysis of these mutants reveals the bioconversion of the OA-6129 compounds: OA-6129 A > B2 -> Bl -> C. Based on the enzymological studies of A933 acylase and the observations on carbapenem fermentation together with the bioconversion of OA-6129 carbapenems, a biosynthetic map which covers almost all of the naturally-occurring carbapenems was constructed. This map clarifies the biosynthetic pathway for carbapenems: for instance, OA-6129 A is hydroxylated at C-8; isomerized at C-6; and then sulfonated at C-8, giving OA-6129 B2, Bl, and C, respectively, and the individual OA-6129 compounds are also catalyzed by A933 acylase, yielding PS-5 and the related carbapenems. As a result of this biosynthetic information, it was possible to specifically produce OA6129 B2 on a practical scale using the OA-6129 A and B2 producing mutant under highly-aerated conditions. In addition to the conventional mutagenesis, a host vector system was established using carbapenem-producing and nonproducing S.fulvoviridis and vectors such as pIJ922 and pIJ702. Protoplast regeneration was useful for increasing the transformation frequencies. Abridged Author's Abstract Strain SF2457, A new producer of amicetin group antibiotic
Miyadoh, S., S.Amano and T.Shomura Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd., 760 Morooka, Kohaku-ku, Yokohama 222, Japan Actinomycetologica, 4: 85-88, 1990 Taxonomic characteristics of strain SF2457, an actinomycete isolated from soil (Mie Prefecture, Japan) and producing a new nucleoside antibiotic, closely related to the actinomycetin group and formed by members of the genera Streptomyces and Arthrobacter, are illustrated. The isolate shows fragmentation of the vegetative mycelium, aerial spore formation, red colouring of the aerial growth and no melanin production. Casein, hypoxanthine and tyrosine are utilized, aesculin is hydrolyzed and the strain is resistant to lysozyme. The isolate has wall chemotype IV, whole cell sugar pattern A and a type PII phospholipid pattern. Mycolic acids are present and MK-8(H4) is the major menaquinone. G+C content equals 66 mol%. On these bases the authors attribute strain SF2457 to Nocardia brasiliensis. The strain is deposited at the Institute for Fermentation, Osaka, Japan with the accession number IFO 15008.
According to the authors this is the first report on the production of amicetin antibiotics by Nocardia. R.L. Effect of adenine and related compounds on spore formation and thiostrepton production by purine mutants of Streptomyces azureus ATCC 14921 Ogata, S., K.Doi and S.Yamada
Microbial Genetics Division, Institute of Genetic
Resources, Actinomycetologica, 4: 89-91, 1990 In the course of an analysis of the accumulation mechanisms of endogenous AICAR (5'-phosphoribosyl-5-amino-4-imidazole carboxamide) and of AIR (5'phosphoribosyl-5-aminoimidazole) and their modes of action on the blocked production of spores and of thiostrepton, the authors investigated the behaviour of two mutants of Streptomyces azureus, ATCC 14921. One strain (Ade2) accumulates AIR due to lack of carboxylase activity, while the second (ATH) accumulates AICAR because of lack of formyltransferase activity. Both mutants require adenine and other purines for growth (50 ug/ml), however excess of adenine and of hypoxanthine inhibits sporulation. AICA (5-amino-4-imidazole carboxamyde), an adenine related compound, suppresses the inhibitory effect of adenine and of hypoxanthine.
Excess adenine increases accumulation of AICAR in mutant ATH and induces accumulation of AICAR in Ade2. Hypoxanthine excess increases the accumulation of AICAR in ATH, but not in Ade2, where it enhances accumulation of AIR.
The inhibitory effect of excess adenine and hypoxanthine on sporulation is proportional to the amount of accumulated AICAR and of AIR. Correlation between AICAR accumulation and depressed sporulation suggests its implication. In addition AIR seems to inhibit spore formation in Ade2.
Adenine and hypoxanthine accumulation appears to affect the purine biosynthetic pathway, resulting in abnormal accumulation of AICAR and of AIR, with consequent effects on sporulation. R.L. PCR conditions for a GC-rich gene Sakata, N., S.Ikeno and M.Hori Showa College of Pharmaceutical Sciences, Machida-shi, Tokyo 194, Japan Actinomycetologica, 4: 92-94, 1990 Polymerase chain reaction (PCR) conditions, suitable for amplifying and cloning G+C-rich organisms, such as streptomycetes, are illustrated. Experimental work was carried out on Streptomyces globisporus, strain C-1020. R.L. Application of actinomycetes in the production of pravastatin, a novel cholesterol-lowering agent
Arai, M., A.Naito, T.Okazaki, N.Serizawa and SIwado Fermentation Research Laboratories, Sankyo Co., Ltd., 2-58, Hiromachi-l-chome, Shinagawa-ku, Tokyo 140, Japan Actinomycetologica, 4: 95-102, 1990 Pravastatin is a tissue-selective inhibitor of HMG-CoA reductase, a key enzyme in cholesterol biosynthesis. This compound was obtained by the microbial hydroxylation of mevastatin(ML-236B). Pravastatin was first discovered in the urine of dog as a minor active metabolite of mevastatin. Various fungi were tested for their ability to transform the substance and it was found that some Mucor hiemalis isolates converted mevastatin mainly to pravastatin. These fungi, however, could not tolerate increased amounts of mevastatin in the culture broth. Amycolata autotrophica strains, isolated from a soil sample collected in Australia, were found to have strong transformation activity of byproduct in spite of tolerating the substrate. After further screening for fresh isolates of actinomycetes, Streptomyces carbophilus was discovered as a potent converter with a limited amount of byproduct. S.carbophilus also tolerated a high amount of mevastatin in the culture broth. Thus S. carbophilus which is capable of pravastatin production on an industrial scale was isolated from a soil sample collected in Australia. The hydroxylation of mevastatin to pravastatin by S. carbophilus was catalyzed by a cytochrome P-450sca monooxygenase system. The P-450sca system was found to exist in the soluble fraction and to be composed of only two components, P450sca and flavoprotein. Therefore, a novel character of the P-450sca system in prokaryote is suggested. Abstract Abridged, R.L. Selective isolation methods and distribution of soil actinomycetes Hayakawa, M.
Department of Fermentation Technology, Actinomycetologica, 4: 103-112, 1990 Isolation of actinomycetes is an indispensable step in the screening programs for industrially useful strains as well as in the ecological study of microorganisms. During the past 10 years, the author and his co-workers have studied selective isolation methods for soil actinomycetes. A new medium (HV agar containing humic acid as sole CN source) and a variety of new methods (including spore activation, elimination of bacteria, dry heating, phenol treatment, chemotaxis, pollen baiting and drying, and use of HV agar supplemented with antibiotics) were developed for the preferential isolation of common and .particular genera (Micromonospora, Microbispora, Streptosporangium, Dactylosporangium, Microtetraspora viridis group and actinoplanetes) of actinomycetes. In addition, some ecological factors (soil pH, humus content, heavy metal pollution, etc.) affecting the distribution of these organisms in soils were clarified. Abstract Abridged, R.L. Dr. Shinobu and Actinomycetes
Muto, N. Department of Biotechnology, Research Center, Toyo Jozo Co., Ltd., 632-1, MiCuku, Ohito-cho, Tagata-shun, Shizuoka 410-23, Japan Actinomycetologica, 4: 113-118, 1990 Dr. Shinobu was honoured for his distinguished contributions to science by the Society for Actinomycetes, Japan. This paper, outlining his life and research work on actinomycete researches of Dr. Shinobu, consists of 1) personal history, 2) starting point of studying actinomycetes, 3) studies on the establishment of criteria for the identification of actinomycete species, 4) summary of the studies on actinomycetes. Abstract Abridged, R.L. Copyright 1991 C.E.T.A., The International Centre for Theoretical and Applied Ecology, Gorizia. |
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