臺灣博碩士論文加值系統

土壤中的放線菌以鏈黴菌 (Streptomyces spp.) 為主，已有許多報告指出，鏈黴菌可拮抗多種植物病原菌，且對植物生長有促進的效果，具有多重的生物防治機制；而其中的二次代謝產物，包括可分解各種物質之酵素與抗生物質，使其被廣泛應用於醫藥、家畜飼料的添加物、殺蟲劑以及植物保護用途上。本研究自台灣各地區分離到 138 株放線菌，初步測試並篩選出 10 株具有拮抗活性的菌株，利用形態學與分子生物學鑑定得知皆為鏈黴菌屬，且其中有些菌株可分泌幾丁質與澱粉分解酵素。測試此 10 株鏈黴菌對植物病原真菌與細菌之生長抑制效果，得知 A272 與 A463 兩菌株對病原真菌之拮抗活性最佳，而 A337 菌株的抗細菌能力最強。此外，探討固態與液態培養基中添加不同碳素源對 A272、A337 及 A463 等 3 株菌株之生長與拮抗活性的影響，結果指出此 3 種鏈黴菌對碳素源的利用有明顯差異；以SEM 觀察固態培養，顯示此 3 株鏈黴菌於添加不同碳素源培養基上之分化形態不同，如於阿拉伯糖培養基中可大量產孢，在添加葡萄糖培養基上則有延遲產孢的傾向，而乳糖對供試菌株為利用速度緩慢的碳素源。測試添加不同碳素源對拮抗活性之影響，得知 A272 菌株除木糖外，於其他供試碳素源的培養基上皆可抑制立枯絲核菌之菌絲生長；A337 菌株僅於添加阿拉伯糖與葡萄糖培養基產生抑菌活性；而A463 菌株於阿拉伯糖培養基上的拮抗能力最強，然有些碳素源雖能促進菌株生長，但無法產生拮抗物質。本研究之結果證實形態分化與抗生物質之產生並無直接相關。
選取較具拮抗效果的 A272 菌株進行發酵與抗生物質分析試驗。在測試最佳培養條件試驗中，針對接種源濃度、pH、發酵時間及光照等因子對菌株生長量、pH變動及抗生活性的影響，進行測試。顯示 A272 菌株以 106 cfu/ml 接種於 pH5的PDB 液態培養基中震盪培養，培養至第 6 天時即表現高抑菌活性，其抑制範圍可達 1.2 cm。此外，培養濾液經不同熱處理後其抗生活性雖略為降低約30%，但顯示當溫度高於 40℃ 時，抑制活性並無明顯變化，此結果證實濾液中可能含有耐熱性抗生物質。利用 A272菌株發酵液進行溫室防治試驗，評估 A272 菌株防治白菜幼苗立枯病與白菜炭疽病的成效，針對幼苗立枯病的防治效果，以稀釋10倍之培養液較能增加葉用白菜三鳳與坂田交配品種播種於感染土後之存活率，各可提高 25.9% 及 41.6 %；而稀釋 100 倍之濾液則對移苗後的防治成效較佳，於三鳳與坂田交配品種各可提升 53.1% 與 50% 的存活率。根據防治白菜炭疽病的結果，顯示施用稀釋 100 倍培養液之效果最好，可降低其罹病度約 53%。
在鏈黴菌之拮抗性代謝產物分析結果中，A272 菌株培養液經乙酸乙酯進行液相萃取分割後，指出乙酸乙酯層與水層均具拮抗活性，乙酸乙酯層之抗菌活性於管柱層析 (Silica) 後的 100%甲醇沖提部中會出現，而水層中的主要抗菌物質則在60-70% 甲醇/水流動相進行管柱層析 (C18) 時可被帶出，因此，推測拮抗物質為偏高極性。以 HPLC 進一步分離並測試生物活性後，得知其抑菌效果可能來自多種拮抗物質結合所產生。分離出具抗菌活性之波峰 P14-4、P11 與 P1，經由1H NMR 與 GC/MS 分析後推測為混合物，包含核苷酸類、糖類、IAA、尿素、quinoline、cholestane及有機酸化合物等，然比對的結果中以糖類佔大多數，其次為長鏈化合物及核酸類，上述化合物或其衍生物均有抗真菌的相關報導，顯示 A272 菌株具有產生多種拮抗物質的特性。
本研究自台灣田間分離到 10 株具拮抗潛力之鏈黴菌，並了解其形態學與生理生化特性；此外，針對部份菌株探討碳素源對其生長與拮抗活性之影響，建立其液態培養所需最適條件，並於溫室條件下測試防治植物病害之成效；最後，分析鏈黴菌 A272 菌株之有效代謝產物的可能種類。本研究所得到的研究成果，祈能有助於未來進一步研發植物保護製劑之用。

Actinomycetes are widely distributed gram-positive filamentous bacteria with varied morphology. The genus Streptomyces is the main group among actinomycetes. Many reports indicate that Streptomyces can protect crops from pathogens and promote plant growth with multiple biocontrol mechanisms. The characters of numerous seconday metabolites biosynthesis, including enzymes and antibiotics, have been in commercial use in medicine, animal feeder additives, insecticides, and plant protection. This study was aimed to screen for antagonistic actinomycete strains with potential application as a biological agent. A total of 138 actinomycetes isolated from different areas in Taiwan were screened for their antagonistic activity against plant pathogens. Ten antagonistic strains were selected and identified as Streptomyces based on morphology, physiological properties and 16S rRNA. Some of them can secrete chitinase and amylase. According to the inhibition spectrum of Streptomyces sp. strains against plant pathogens, A35, A272 and A463 strains are superior in antifungal activity；A337, A377 and A454 strains have antibiotics against bacteria. The onset of antibiotic biosynthesis is determined and influenced by a variety of physiological and environmental factors. The most important medium component for growth and secondary metabolite formation is the carbon source. Investigating the influence of carbon sources on growth and antibiotic activity of Streptomyces sp. on medium and in submerged culture. According to the results, utilization of carbon sources depends on species. Morphological differeation and degrees of antifungal activity of A272 strain are varied on ISP9 basal medium and medium contained 1% arabinose, fructose, glucose, inositol, lactose, mannitol, sucrose, and xylose.
One promising strain, Streptomyces sp. A272 with strong antifungal activity was selected for the further studies. After investigating the influence of initial inoculum, pH, time course, and light on the growth and antibiotic activity in liquid culture, the results revealed that the optimum condition for growth and antibiotic activity was added 106 cfu/ml inoculum in pH 5 PDB medium, and the antibiotic activity would be detected after 6 days cultured. The thermostability of the antibiotic activity in crude culture supernatant was examined. Although the antifungal activity are slightly decreased after heat treatments, the antifungal activity did not be affected between different heat treatments. A preliminary trial on the disease control efficacy indicated that the infection of R. solani AG4 and C. higginsianum on Brassica rapa L. (Chinese Group) was greatly reduced by drenching and spraying application of the broth culture. 100X-diluted A272 broth culture increased more percentage of survival of 7-days-old seedlings in infested soil；however,10X-diluted A272 broth culture was more effective on controlling damping-off disease after seed sowed. The application of 100X-diluted A272 broth culture reduced more disease index percentage of anthracnose infection than 10X-diluted broth, and the broth is much more effective than filtrate on disease controlling anthracnose and damping-off in green house.
After analysis of antifungal metabolites against R. solani AG4 and C. gloeosporioides of A272 strain, the results indicated that A272 strains produced multiple water-soluble antibiotics with broad spectrum of activity, contained α-D-glucopyranoside, nucleoside antibiotics, urea, IAA, quinoline, cholestane and organic acid. Thus, the antagonistic activity of A272 strain is considered that all of secondary metabolites join in a common effect. It could decrease the risk of resistance in pathogen.

中文摘要……………………………………………………………………………………i
英文摘要…………………………………………………………………………………..iii
目次………………………………………………………………………………………...v
表目次…………………………………………………………………………………....viii
圖目次……………………………………………………………………………………..ix
前言……………………………………………………………………………………..1
材料與方法……………………………………………………………………………..7
一、具拮抗潛力之鏈黴菌的篩選與鑑定……………………………………………..7
(一) 鏈黴菌菌株的來源、分離保存及抗生活性測試……………………………7
(二) 供試放線菌之鑑定………………………….. ……………………………….7
1. 分子生物學鑑定…………………………………………………………....7
2. 形態學暨生理生化鑑定……………………………………………………8
(1) 形態觀察…………………………………………………………………...8
(2) 培養性狀…………………………………………………………………...9
(3) 碳素源的利用……………………………………………………………...9
(4) 黑色素的形成……………………………………………………………...9
(5) 澱粉酶與幾丁質分解酵素產生測定…………………………………….10
(三) 抑菌族譜之建立…..………………………………………………………...10
1. 對植物病原真菌之拮抗性測試…………………………………………..10
2. 對植物病原細菌之拮抗性測試……………………………………..……11
二、 探討碳素源對於鏈黴菌生長與抗生活性的影響……………………………...11
(一) 供試菌株孢子懸浮液之製備……………………………………………….11
(二) 以掃描式電子顯微鏡觀察碳素源對鏈黴菌氣生菌絲生長之影響……….12
(三) 探討不同碳素源對鏈黴菌拮抗R. solani AG4 RST-04之影響……...........12
三、 A272 菌株產生之抑菌代謝物的分離與分析…………………………………13
(一) A272 菌株接種源之製備與分析………………………...………………...13
(二) 生長乾重之測定………...………………………………………………….13
(三) 抑菌活性之測試……………………….……………………………………14
(四) 評估不同培養條件對A272菌株的生長與培養濾液的抑菌效果…….….14
(五) 評估溫室中利用 A272 菌株培養液防治作物病害………………………15
　　 1. 防治白菜幼苗立枯病之評估……………………………………………15
2. 防治白菜炭疽病之評估…………………………………………………16
(六) A272菌株發酵液中有效抑菌成分的分析…………………………………17
1. A272鏈黴菌培養液萃取物製備與生物活性分析………………………17
2. A272 菌株發酵液之液相—液相萃取分劃………………………...…....17
3. 活性成分分離與分析……………………………………………………18
四、統計分析…………………………………………………………………………..19
結果…………………………………………………………………………………….20
一、具有生物防治潛力之鏈黴菌的分離與鑑定……………………………………..20
(一) 菌株之分離與篩選………………………………………………………….20
(二) 供試鏈黴菌之鑑定………………………………………………………….20
1. 分子生物學鑑定…………………………………………………………..20
2. 放線菌菌株的傳統鑑定…………………………………………………..21
(1) 形態觀察………………………………………………………………….21
(2) 培養性狀………………………………………………………………….21
(3) 碳素源的利用…………………………………………………………….22
(4) 黑色素的形成…………………………………………………………….23
(5) 澱粉酶與幾丁質分解酵素產生測定…………………………………….23
(三) 抑菌族譜之建立…………………………………………….……………...23
二、探討碳素源對於供試菌株生長及拮抗能力的影響…………………………..…24
(一) 不同碳素源於固態培養下對鏈黴菌生長與抗生活性之影響………….…24
(二) 不同碳素源於液態培養下對鏈黴菌生長與抗生活性之影響………….…25
三、A272 菌株產生之抑菌代謝物的分離與分析……………………………………26
(一) 評估不同培養條件對 A272 菌株生長與濾液抑菌效果之影響………....26
(二) 評估 A272 菌株培養液於防治作物病害之效果…………………………27
(三) A272發酵液中有效抑菌成分之分析………………………………………28
1. A272鏈黴菌培養液萃取物製備與生物活性分析……………………..…28
2. 液相-液相萃取分劃試驗與活性分析…………………………………….29
3. 活性成分分離與分析……………………………………………………..29
討論…………………………………………………………………………………….32
參考文獻……………………………………………………………………………….40
圖表…………………………………………………………………………………….47
附錄…………………………………………………………………………………...101

杜金池、謝廷芳。1994。百合白絹病之發生與防治。臺灣花卉病蟲害研討會專刊。11-22頁。
梅澤純夫。1953。抗菌性物質。培風館。東京。320頁。
廖龍盛。1990。實用農藥。台灣省農林廳。台中。885頁。
Akira E, Kazuo K, Tomomasa M, 1970. Mechanism of action of the antifungal agent polyoxin D, 1970. The Journal of Bacteriology 104, 189-96.
Avis TJ, Belanger RR, 2001. Specificity and mode of action of the antifungal fatty acid cis-9-heptadecenoic acid produced by Pseudozyma flocculosa. Applied and environmental microbiology 67, 956-60.
Barna JCJ, Williams DH, 1984. The structure and mode of action of glycopeptide antibiotics of the Vancomycin Group. Annual Review of Microbiology 38, 339-57.
Ben-Fguira LF, Fosto S, Mehdi RB, Mellouli L, Laatsch H, 2005. Purification and structure elucidation of antifungal and antibacterial activities of newly isolated Streptomyces sp. strain US80. Research in Microbiology 156, 341-7.
Benson DR, Silvester WB, 1993. Biology of Frankia strains, actinomycete symbionts of actinorhizal plants. Microbiological Reviews 57, 93-319.
Bhavanani SM, Ballow CH, 2000. New agents for gram-positive bacteria. Current Opinion in Microbiology 3, 528-34.
Black MC, Beute MK, 1985. Soil components that affect severity of Cylindrocladium black rot on peanuts. Plant Disease 69, 36-9.
Blanchette RA, Sutherland JB, Crawford DL, 1981a. Actinomycetes in discolored wood
of living silver maple. Canadian Journal of Botany 59, 1-7.
Blanchette RA, Sutherland JB , Crawford DL , 1981b. The role of actinomycetes in the
discoloration and decay process of living silver maple trees. Phytopathology 71, 204.
Chater KF, Bibb MJ, 1997. Regulation of bacterial antibiotic production. In Rehm HJ, Reed G, eds. Products of Secondary Metabolism. Weinheim: VCH, 57-105.
Cook RJ, 2000. Advances in plant health management in the 20th century. Annual Review of Phytopathology 38, 95-116.
Conn VM, Walker AR, Franco CM, 2008. Endophytic actinobacteria induce defense pathways in Arabidopsis thaliana. Molecular Plant Microbe Interaction 21, 208-18.
Crawford DL, Biodegradation of agricultural and urban wastes. 1988. In: Goodfellow M, Williams ST, Mordarski M eds. Actinomycetes in biotechnology. San Diego: Wiley Interscience, 433-59.
Crawford W, 1995. Characterization of Streptomyces lydicus WYEC108 as a potential biocontrol agent against fungal root and seed rots. Applied and Environmental Microbiology 61, 3119-28.
Demain AL, Aharonowitz Y, Martin JF, 1983. Metabolic control of secondary biosynthetic pathways. In: Vining LC, eds. Biochemistry and Genetic Regulation of Commercially Important Antibiotics. London: Addison-Wesley Publications, 49-72.
Easterly WD, Jordin MW, Dorsey WS, Clark G, 1965. Synthesis and antifungal activity of some amide and urea derivatives of bromal and dichloroacetaldehyde.
Journal of Pharmaceutical Sciences 54, 1358-61.
Ebben MH, Spencer DM, 1978. The use of antagonistic organisms for the control of black root rot of cucumber, Phomopsis sclerotioides. Annuls of Applied Biology 89, 103-6.
El-Abyad MS, El-Sayed MA, El-Shanshoury AR, El-Sabbagh SM, 1996. Antimicrobial activities of Streptomyces pulcher, S. canescens and S. citreofluorescens against fungal and bacterial pathogens of tomato in vitro. Folia Microbiol (Praha) 41, 321-8.
Elmegeed GA, Wardakhan WW, Younis M, Louca NA, 2004. Synthesis and antimicrobial evaluation of some novel cholestane heterocyclic derivatives, Archiv der Pharmazie - Pharmaceutical and Medicinal Chemistry 337, 140-7
El-Mehalawy AA, Gebreel HM, Rifaat HM, El-Kholy IM, Humid AA, 2008. Effect of antifungal compounds produced by certain bacteria on physiological activities of human and plant pathogenic fungi. Journal of Applied Sciences Research 4, 425-32.
El-Naggar MY., Hassan MA, Said WY, El-Aassar SA, 2003. Effect of support materials on antibiotic MSW2000 production by immobilized Streptomyces violatus. The Journal of General and Applied Microbiology 49, 235-43.
Ensign JC, 1978. Formation, properties, and germination of actinomycete spores. Annual Review of Microbiology 32, 185-219.
Garcia-Dominguez M, Martin JF, Liras P, 1989. Characterization of sugar uptake in wild-type Streptomyces clavuligerus, which is impaired in glucose uptake, and in a glucose-utilizing mutant. Journal of Bacteriology 171, 6808-14.
Georgiou CD, Patsoukis N, Papapostolou I, Zervoudakis G, 2006. Sclerotial metamorphosis in filamentous fungi is induced by oxidative stress. Integrative and Comparative Biology 46, 691-712.
Gottlieb E, 1966. Methods for characterization of Streptomyces species. International Journal of Systematic Bacteriology 3, 313-40.
Gupte M, Kulkarni P, Ganguli BN, 2002. Antifungal antibiotics. Applied Microbiology and Biotechnology 58, 46-57.
Guzmán S, Ramos I, Moreno E, Ruiz B, Rodríguez-Sanoja R, Escalante L, Langley E, Sanchez S, 2005. Sugar uptake and sensitivity to carbon catabolite regulation in Streptomyces peucetius var. caesius. Applied Microbiology and Biotechnology 69, 200-6.
Hall V, 2008. Actinomyces--gathering evidence of human colonization and infection.
Anaerobe 14, 1-7.
Hancock REW, Chapple DS, 1999. Peptide antibiotics. Antimicrobial Agents and Chemotherapy 43, 1317-23.
Harman JW, Masterson JG, 1957. The mechanism of nystatin action. Irish Journal of Medical Science 32, 249-53.
Hatano K, 2001. Chapter 9. Family Streptomycetaceae. In: The Society for
Actinomycetes eds. Identification Manual of Actinomycete. Tokyo, Japan: Business Center for Academic Societies Japan, 249-57.
Hiltunen LH, Ojanpera¨ T, Kortemaa H, Richter E, Lehtonen MJ, Valkonen JPT, 2009. Interactions and biocontrol of pathogenic Streptomyces strains co-occurring in potato scab lesions. Journal of Applied Microbiology 106, 199-212.
Hopwood DA, Sherman DH, 1990. Molecular genetics of polyketides and its comparison to fatty acid biosynthesis. Annual of Review of Genetics 24, 37-66.
Hsin DS, 2003. Control of crop disease with Streptomyces padanus PMS-702 and identification of fungichromin as its major antifungal metabolite related to suppress plant pathogens. Taiwan, ROC: National Chung Hsing University.
Hutchinson CR, 1999. Microbial polyketide synthases: more and more prolific. Proceedings of the National Academy of Sciences of the United States of American 96, 3336-8.
Imriskova I, Roberto AE, Silvia G, Romina RS, Elizabeth L, Sergio S, Lai WR, 2003. Development of Streptomyces griseobrunneus S3 as a bioagent for the control of plant fungal disease. Taiwan, ROC: National Chung Hsing University.
Iznaga Y, Lemus M, Gonzalez L, Garmendia L, Nadal L, Vallin C, 2004. Antifungal activity of actinomycetes from Cuban soils. Phytotherapy reserch 18, 494-6.
Jonsbu E, McIntyre M, Nielsen J, 2002. The influence of carbon sources and morphology on nystatin production by Streptomyces noursei. Journal of Biotechnology 2, 133-44.
Kabir AKMS, Dutta P, Anwar MN, 2005. Antimicrobial Evaluation of Some Decanoyl Derivatives of Methyl α-D-Glucopyranoside International Journal of Agriculture & Biology. International Journal of Agriculture and Biology 5, 760-3.
Kennedy BW, Alcorn SM, 1980. Estimates of US crop losses to procaryote plant
pathogens. Plant Disease 64, 674-6.
Kieser T, Bibb MJ, Buttner M, Chater KF, Hopwood DA, 2000. Practical Streptomyces genetics. Norwich, England: The John Innes Foundation Norwich.
Kimura K, Bugg TDH, 2003. Recent advances in antimicrobial nucleoside antibiotics targeting cell wall biosynthesis. Nature Product Report 20, 252-73.
Kintro M, Lignell U, Hirvonen MR, Nevalainen A, 2005. pH effects on 10 Streptomyces spp. growth and sporulation depend on nutrients. Letters in applied microbiology 41 32-8.
Kiyoshi I, 1988. Nucleotide antibiotics : structure, biological activity, and biosynthesis 12, 1711-39.
Lahdenperä ML, 1987. The control of Fusarium wilt on carnation with a Streptomyces preparation. Acta Horticulturae 216, 85-92.
Lai WR. 2003. Development of Streptomyces griseobrunneus S3 as a bioagent for the control of plant fungal diseases. Taiwan, ROC: National Chung Hsing University.
Lancini GL, Parenti F, Gallo GG, eds, 1995. Antibiotics : A multidisciplinary approach. New York: Plenum Press.
Lechevalier MP, Lechevalier HA, 1980. The chemotaxonomy of actinomycetes. Journal of carbohydrate chemistry 16, 1029-49.
Len C, Postel D, Ronco G, Villa P, 1997. Synthesis of bis (Carbamoyl Ester) derivatives of D-Glucose as antifungal products. Journal of Carbohydrate Chemistry 16, 1029-49.
Liu D, Anderson NA, Kinkel LL, 1995. Biological control of potato scab in the field with Streptomyces spp. Phytopathology 85, 827-31.
Loria R, Kers J, Joshi M, 2006. Evolution of plant pathogenicity in Streptomyces. Annual Review of Phytopathology 44, 469-87.
Manteca A, Alvarez R, Salazar N, Yague P, Sanchez J, 2008. Mycelium differentiation and antibiotic production in submerged cultures of Streptomyces coelicolor. Applied and Environmental Microbiology 74, 3877-86.
Masanori S, Osamu N, 1990. Streptomycin: biosynthesis and self-resistance mechanism in streptomycin-producing Streptomyces griseus. Actinomycetologica 4, 15-22.
Meyers A, 2003. Rapid identification of filamentous actinomycetes to the genus level using genus-specific 16S rRNA gene restriction fragment patterns. International Journal of Systematic and Evolutionary Microbiology 53, 1907-15.
Miyadoh S, eds, 1997. Atlas of Actinomycetes. The Society for Actinomycetes Japan, Co., Ltd. 223. Asakura Publishing.
Musiol R, Jampilek J, Buchta V, Silva L, Niedbala H, Podeszwa B, Palka A, Majerz-Maniecka K, Oleksyn B, Polanski J, 2006, Antifungal properties of new series of quinoline derivatives, Bioorganic and Medicinal Chemistry 14, 3592-8.
Nourozian J, Etebarian HR, Khodakaramian G., 2006. Biological control of Fusarium graminearum on wheat by antagonistic bacteria Songklanakarin. Journal of Science and Technology 28, 29-38.
Pal KK, McSpadden Gardener B, 2006. Biological control of plant pathogens. The Plant Health Instructor 10, 1-25
Pamboukian CRD, Facciotti MCR, 2004. Production of the antitumoral retamycin during continuous fermentations of Streptomyces olindensis. Process Biochemistry 39, 2249-55.
Park CN, Lee JM, Lee D, Kim BS, 2008. Antifungal activity of valinomycin, a peptide antibiotic produced by Streptomyces sp. strain M10 antagonistic to Botrytis cinerea. Journal of Molecular Microbiology and Biotechnology 18, 880-4.
Park Y, Tamura S, Koike Y, Okabe M, 1997. Mycelial pellet intrastructure visualization and viability in a culture of Streptomyces fradiae using confocal scanning laser microscopy. Journal of Fermentation and Bioengineering 84, 483-6.
Perlman D, 1979. Use of antibiotics in cell culture media. In: Methods in Enzymology 58, 110-6.
Piepersberg W, 1995. Streptomycin and related aminoglycosides. Biochemistry and Genetics of Antibiotic Production, Newton, MA: Butterworth-Heinemann, 531-70.
Rokem JS, Lantz AE, Nielsen J, 2007. Systems biology of antibiotic production by microorganisms. Nature Product Report 24, 1262-87.
Rothrock CS, Gottlieb D, 1984. Role of antibiosis in antagonism of Streptomyces hygroscopicus var. geldanus to Rhizoctonia solani in soil. Canadian Journal of
Microbiology 30, 1440-7.
Rueda BE, Miguelez M, Hardisson C, Manzanal MB, 2001. Mycelial differentiation and spore formation by Streptomyces brasiliensis in submerged culture. Canadian Journal of Microbiology 47, 1042-7.
Sabaratnam S, Traquair JA, 2002. Formulation of a Streptomyces biocontrol agent for the suppression of Rhizoctonia damping-off in tomato transplants. Biological Control 23, 245-53.
Sanchez L, Brana AF, 1996. Cell density influences antibiotic biosynthesis in Streptomyces clavuligerus. Microbiology 142, 1209-20.
Sanchez S, Demain AL, 2002. Metabolic regulation of fermentation processes. Enzyme and Microbial Technology 31, 895-906
Shih HD, Liu YC, Hsu FL, Mulabagal V, Dodda R, Huang JW, 2003. Fungichromin: a substance from Streptomyces padanus with inhibitory effects on Rhizoctonia solani. Journal of Agricultural and Food Chemistry 51, 95-9.
Shirling EB, Gottlieb D, 1966. Methods for characterization of Streptomyces species. International Journal of Systemtic Bacteriology 16, 313-40.
Siddiqui ZA, Mahmood I, 1999. Role of bacteria in the management of plant parasitic nematodes : A review. Bioresource Technology 69, 167-79.
Strzelczyk E, Kampert M, Michalski L, 1985. Production of cytokinin-like substances by mycorrhizal fungi of pine (Pinus sylvestris L.) in cultures with and without metabolites of actinomycetes. Acta Microbiologica Polonica 34, 177-85.
Sugimoto M, Fukami S, Kayakiri H, Yamazaki S, Matsuoka N, Uchida I, Mashimo T, 2002. The β-lactam antibiotics, penicillin-G and cefoselis have different mechanisms and sites of action at GABAA receptors. British journal of pharmacology 135, 427-32.
Tuomi T, Laakso S, Rosenqvist H, 1994. Indole-3-acetic acid (IAA) production by a biofungicide Streptomyces griseoviridis strain. Annales Botanici Fennici 31, 59-63.
Ueda K, Matsuda K, Takano H, Beppu T, 1999. A putative regulatory element for carbon-source-dependent differentiation in Streptomyces griseus. Microbiology 145, 2265-71.
Vw C, 1961. Physiology of actinomycetes. Annual Review of Microbiology 15, 1-26.
Wardell, JN, Stocks SM, Thomas CR, Bushell ME, 2002. Decreasing the hyphal branching rate of Saccharopolyspora erythraea NRRL 2338 leads to increased resistance to breakage and increased antibioticproduction. Biotechnology and Bioengineering 78,141-6.
Watson ET, Williams ST, 1974. Studies on the ecology of actinomycetes in soil. VII. Actinomycetes in a coastal sand belt. Soil Biology and Biochemistry 6, 43-52.
Weisblum B, 1995. Insights into Erythromycin action from studies of its activity as inducer of resistance. Antimicrobial Agents and Chemotherapy 39, 797-805.
Weissman J, 2001. Polyketide biosynthesis: a millennium review. Nature Product Report 18, 380-416.
Williams RR, 1965. The effect of summer nitrogen application on the quality of apple blossoms. Journal of Horticultural Science 40, 31-41.
Williams ST, Goodfellow M, Alderson G, 1989. Genus Streptomyces Waksman and Henrici 1943, 339AL. In: Williams ST, Sharpe ME, Holt JG eds. Bergey''s Manual of Systematic Bacteriology 4, Williams and Wilkins, Baltimore, 2452-92.
Williams ST, Vickers JC, 1988. Detection of actinomycetes in the natural environment. problems and perspectives. In: Okami Y Beppu T, Ogawa H eds. Biology of Actinomycetes 88. Japan: Scientific Soc Press, 265-70.
Yang YK, Morikawa M, Shimizu H, Shioya S, Suga KI, Nihira T, Yamada Y, 1996. Image analysis of mycelial morphology in virginiamycin production by batch culture of Streptomyces virginiae. Journal of Fermentation and Bioengineering 81, 7-12.
Yoo JC, Han JM, Nam SK, Baik KS, Jo JS, Seong CN, 2002. Characterization of a streptomycete isolate producing the potent cytotoxic substance, nonadecanoic acid. Journal of Microbiology 40, 178-81.
Yu J, Liu Q, Liu Q, Liu X, Sun Q, Yan J, Qi X, Fan S, 2008. Effect of liquid culture requirements on antifungal antibiotic production by Streptomyces rimosus MY02. Bioresource Technology 99, 2087-91.
Zakeri B, Wright GD, 2008. Chemical biology of tetracycline antibiotics. Biochemistry and Cell Biology 86, 124-36.