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SIMPULAN

Isolasi kapang endofit dari tanaman obat yang berasal dari Lombok Timur Nusa Tenggara Barat dan penapisan sitotoksisitasnya menghasilkan kapang Curvularia lunata BioMCC FE-283 sebagai kapang yang dapat menghasilkan metabolit paling aktif dan mampu menghambat proliferasi sel kanker payudara MCF-7 secarain-vitro.Senyawa aktif kapang endofitC. lunata mampu menghambat 28 % pertumbuhan sel kanker MCF-7 pada konsentrasi 5 mg/L.

Senyawa aktif yang dihasilkan oleh kapang C. lunata BioMCC FE-00283 adalah 8-hydroxy 9,12-octadecadienoic acid (8-HODE) yang merupakan senyawa kelompok oksilipin. Senyawa 8-HODE mempunyai rumus molekul C18H32O3dengan bobot molekul 296.

Senyawa 8-HODE diproduksi oleh C. lunata pada fermentasi kultur terendam. Komponen media kultivasi yang secara nyata mampu meningkatkan produksi 8-HODE adalah glukosa sebagai sumber karbon, monosodium glutamat sebagai sumber nitrogen dan minyak jagung sebagaiinducer. Optimasi komposisi media mampu meningkatkan produktivitas C. lunata dalam produksi 8-HODE 22 kali lipat dibandingkan dengan media basalnya. Produksi 8-HODE tertinggi pada fermentasi kultur terendam tercapai pada komposisi media yang terdiri dari 5,87 g/L glukosa, 11,01 g/L monosodium glutamat, dan 1,00 ml/L minyak jagung.

SARAN

8-HODE adalah kelompok oksilipin yang dilaporkan mempunyai cakupan bioaktivitas luas baik sebagai antimikroba maupun antikanker. Penelitian lanjutan perlu dilakukan untuk mengetahui bioaktivitas 8-HODE yang lain, baik sebagai antikanker, antimikroba maupun antiplasmodium. Aktivitas anti kanker 8-HODE baru dicoba terhadap satu jenis sel kanker. Uji terhadap sel kanker lain perlu dilakukan untuk melihat spektrum aktivitas senyawa, disamping itu perlu dilanjutkan pengujian terhadap sel kanker payudara pada tingkatin vivo.

Optimasi produksi 8-HODE yang dilakukan dalam penelitian ini masih merupakan model dasar yang datanya diperoleh dari kultivasi kultur kocok. Perlu dilakukan penelitian lanjutan untuk verifikasi hasil optimasi dalam skala

bioreactor terkendali (fermentor). Kultivasi dalam bioreaktor terkendali diharapkan dapat memudahkan untuk optimasi kondisi proses dibandingkan dengan menggunakan kultur kocok.

Akdemir Z, Kahraman C, Tatli II, Akkol EK, Suntar I, Keles H. 2010. Bioassasy- guided isolation of anti-inflammatory, antinociceptive, and wound healer glycosides from flowers of Verbascum mucronatum Lam. [online] doi : 10.1016.05.059. Diakses pada tanggal 10 Maret 2011

Akibonde OA. 2010. Evaluation of antifungal efficacy of some plant extracts on Curvularia lunata, the causal organism of maize leaf spot. African J. Environ. Sci. Tech. 4(11), 797-800

Al-Bari, MAA., MA Sayeed, A Khan, MR Islam, P Khondokar, MMS Rahman, MAU Islam. 2007. In vitro antimrobial activities and cytotoxicity of ethyl acetate extract fromStreptomyces maritimus.Biotechnol.6 (1) : 81-85 Albert A. 1985. Selective toxicity, the physic chemical basic of therapy . 7ed .

London. Chapman and Hall

Amara AA, El-Masry MH, Bogdady HH. 2008. Plant crude extracts could be the solution: extracts showing in vivo antitumorigenic activity. Pakistan. J. Pharm. Sci.21 (2) : 159-171.

Amna, T., RK Khajuria, SC Puri, V Verma, GN Qazi. 2006. Determination and quantification of camptothecin in an endophytic fungus by liquid chromatography –positive mode electrospray ionization tandem mass spectrometry.Current Sci. 91 (2) : 321-324

Anderson JE, Goetz CM, McLaughlin JL, Suffness M. 1991. A blind comparison of simple bench-top bioassays and human tumour cell cytotoxicities as antitumor prescreens.Phytochem Anal. 2 : 107-111

Andreou A, Brodhun F, Feussner I. 2009. Biosynthesis of oxylipins in non- mammals.Prog. Lip. Res. , 48, 148-170

Arjol M, Galia MB, Bermudo E. 2010. Identification of oxylipins antifungal activity by LC-MS/MS from the supernatant of Pseudomonas 42A2. Chem. Phys. Lip.. 163:341-6

Arung ET, Wicaksono BD, Handoko YA, Kusuma IW, Yulia D, Sandra F. 2009. Anti-Cancer Properties of Diethylether Extract of Wood from Sukun (Artocarpus altilis) in Human Breast Cancer (T47D) Cells. Tropic. J. Pharmaceut. Research. 8 (4) : 317-324

Austin JE. 1992. Agroindustrial Project Analysis. Maryland. The John Hopkins University Press.

Azeveda, JL., W Macheroni Jr, JO Perira , WL de Araujo. 2000. Endophytic microorganisms: a review on insect control and recent advances on tropical forest. Electronic. J. Biotechnol. 3 (1) [online] http://www.ejb.org/content/vol3/issue1/full/k. Diakses 26 April 2006

Badalo A, Bastida J, Maximo MF, Hidalgo AM, Murcia MD. 2005. Production of (E) 10 hydroxy-8-octadecadienoic acid with lyophilized microbial cells.Am. J. Biochem. Biotech. 1 (1) : 1-4

Bas D, Boyaci IH. 2007. Modeling and optimization I: Usability of response surface methodology.J. Food Engineer.78 : 836-845

Bezerraa MA, Santelli RE, Oliveiraa EP, Villar LS, Escaleira LA. 2008. Response surface methodology (RSM) as a tool for optimization in analytical chemistry.Talanta.76 : 965–977

Birkett NJ, Campbell CAM, Chamberlain K, Guerrieri E, Hick AJ, Martin JL, Matthews M, Napier JA, Petterson J, Pickett JA, Poppy GM, Pow Em, Pye BJ, Smart LE, Wadhams GH, Wadhams LJ, Woodcock CM. 2000. New roles for cis-jasmone as an insect semiochemical and in plant defense. Proc. Nat. Acad. Sci. USA. 97 : 9329-9334

Blee E. 2002. Impact of phyto-oxylipins in plant defense. TRENDS Plant Sci. 7 (7) : 315-321

Bodalo A, Bastida J, Maximo MF, Hidalgo AM, Murcia MD. 2005. Production of (E) 10-hydroxy-8-octadecenoic acid with lyophilized microbial cells.Am. J. Biochem. Biotechnol. 1(1): 1-4

Bowers WS, Hoch HC, Evans PH, Katayama M. 1986. Thallophytic allelopathy: isolation and identification of laetisaric acid.Sci. 232 : 105-106

Boyd, MR. 2004. The NCI in vitro anticancer drug discovery screen : Concept, implementation and operation. Di dalam : Teicher B (ed). Preclinical screening, clinical trial, and approval. ed 2. Totowa. Humana Press Inc. Brodhun F, Feussner I. 2011. Oxylipins in fungi.FEBS J. , 278, 1047-1063 Cantrell CL, Kniffin TM, Case BP, Duke SO, Mena EE, Wedge DE. 2008.

Isolation and Identification of Antifungal Fatty Acids from the BasidiomyceteGomphus floccosus.J. Agric. Food Chem. 56: 5062– 5068 Caruso, M., AL Colombo, L Fedeli, A Pavesi, S Avaroni, M Saracchi, G

Ventrella. 2000. Isolation of endophytic fungi and actinomycetes taxanes producer.Annal Microbiol. 50 : 3-13

Castillo UF, Strobel GA, Ford EJ, Hesse WM, Porter H, Jensen JB, et al. 2002. Munumbicins wide spectrum antibiotics produced by Streptomyces NRRL 30562 endophytic onKennedia nigricans.Microbiol. 148 : 2675-2685 Chakravarthi, BVSK., Das P, Surendranath K, Karande AA, Jayabaskara V.

2008. Production paclitaxel by Fusarium solani isolated from Taxus celebica. J. Biosci. 33 (2) :00-00. [online] http://www.ias.ac.in/jbiosci. Diakses tanggal 17 Juni 2008

Chen GG, Xu H, Lee JFY, Subramaniam M, Leung KL, Wang SH, Chan UPF, Spelsberg TC. 2003. 15-Hydroxy-eicosatetraenoic acid arrests growth of

colorectal cancer cells via a peroxisome proliferator-activated receptor gamma-dependent pathway.Int. J. Cancer. 107 : 837-843

Chin, YW., MJ Balunas, HB Chai, AD Kinghorn. 2006. Drug discovery from natural sources.The APPS J. 8 (2) : E239-E253)

Christensen SA, Kolomiets MV. 2011. The lipid language of plant-fungal interactions.Fungal Gen. Biol. , 48, 4-14

Claeson P, Bohlin L. 1997. Some aspects of bioassay methods in natural- product research aimed at drug lead discovery.TIBTECH. 15: 245-248 Coetzer RLJ, Haines RLJ, Fatti LP. 2010. Central composite designs for

estimating the optimum conditions for a second-order model. J. Statist. Plann. Inference. [online]. Diambil dari doi : 10.1016/j.jspi.2010.11.026. Diakses tanggal 19 Januari, 2011

Colquhoun A, Miyake JA, Benadiba M. 2009. Fatty Acid, eicosanoids and cancer.Nutrit. Ther. Metabol. 27(3): 105-112

Costa-Lotufo LF, Khan MTH, Ather A, Wilke DV, Jmenez PC, Pessoa C, de Morales MEA, de Moraes MO. 2005. Studies of the anticancer potential of plants used in Bangladeshi folk Medicine.J. Ethnopharmac. 99: 21-30 Cragg, GM., JE Simon, JG Jato, KM Snader. 1996. Drug Discovery and

Development at the National Cancer Institute: Potential for new Pharmaceutical Crops. Didalam: Janick, J (ed). Progress in New Crops. Arlington. ASHS Press. Arlington

Cragg, GM., MR Boyd, R Khanna, R Kneller, TD Mays, KD Mazan, DJ Newman, EA Sausville. 1999. International collaboration in drug discovery and development: the NCI experience.Pure Appl. Chem. 71 (9): 1619-1633 Croteau, R., TM. Kutchan, NG Lewis. 2000. Natural Product (Secondary

Metabolites). Di dalam: Buchanan, B., W Gruissem, R Jones (ed). Biochemistry dan Molecular Biology of Plants. American Society of Plant Physiologist

Daysi, BH., GA Strobel, U Castillo, D Ezra, J Sears, DK Weaver, JB Runyon. 2002. Napthalene, an insect repellent, is produced by Muscodor vitigenus, a novel endophytic fungus.Microbiol.148 : 3737-3741

Ding Q, Yang LX, Yang HW, Wang YF, Wang S. 2009. Cytotoxic and antibacterial triterpenoids derivatives from Clematis ganpiniana. J. Ethnopharmacol. 126 : 382-385

Ding, G., S Liu, L Guo, Y Zhou, Y Che. 2008. Antifungal metabolites from the plant endophytic fungus Pestalotiopsis foedan. J. Nat.Prod. 71 (4) : 615- 618

Eyberger AL., R Dondapati, JR Porter. 2006. Endophyte fungal isolates from Phodophylum peltatum produce podophylotoxin. J. Nat. Prod. 69 (8) : 1121-1124

Ezra D, Castillo UF, Strobel GA, Ford EJ, Hesse WM, Porter H, et al. 2004. Coronamycins peptide antibiotics produced by a VerticillateSterptomyces sp. (MSU-2110) endophytic onMonsterasp.Microbiol. 150 : 785-793 Filip P., RWS Weber, O Sterner, T Anke. 2003. Hormonemate, a new cytotoxic

and apoptosis-inducing compound from the endophytic fungus Hormonema dematioides. I. Identification of the producing strain and isolation and biological properties of hormonemate. Z. Naturforsch. 58c : 547-552

Gangadevi V dan J Muthumary. 2008. Isolation of Colletotrichum gloeosporioides, a novel endophytic taxol-producing fungus from the leaves of a medicinal plant,Justicia gendarusa.Mycol. Balcanica.5 : 1-4 Gangadevi V, M Murugan, J Muthumary. 2008. Taxol determination from

Pestalotiopsis pauciseta, a fungal endophyte of a medicinal plant. Chin. J. Biotech.24 (8) : 1433-1438

Gao H, Liu M, Liu J, Dai H, Zhou X, Liu X. 2009. Medium optimization for the production of avermectin B1a by Streptomyces avermitilis 14-12A using response surface methodology.Bioresource Technol. 100: 4012–4016 Gao X, Kolomiets MV. 2009. Host-derived lipids and oxylipins are crucial signals

in modulating mycotoxin production by fungi.Toxin Reviews , 28(2-3), 79– 88

Gao, XX., H Zhou, DY Xu, CH Yu, YQ Chen, LH Qu. 2005. High diversity of endophytic fungi from the pharmaceutical plant, Heterosmilax japonica Kunth revealed by cultivation-independent approach.FEMS Microbiol. Lett. 249 : 255-266

Gogoi DK., S Mazumder, R Saika, TC Bora. 2008a. Impact of submerged culture condition on growth and bioactive metabolite produced by endophyte Hypocrea spp. NSF-08 isolated from Dillenia indica Linn. in North-east India.J. Med. Mycol. 18 (1) : 1-9

Gogoi DK., HPD Boruah, R Saikia, TC Bora. 2008b. Optimization of process parameters for improved production of bioactive metabolite by a novel endophytic fungus Fusarium sp. DF2 isolated from Taxus mallichiana of North East India.World J Microbiol. Bioetchnol. 24 : 79 – 87

Graner G, Hamberg M, Meijer J. 2003. Screening of oxylipins for control of oilseed rape (Brassica napus) fungal pathogens.Phytochem. 63 : 89-95 Guimarães DO, Borges WS, Kawano CY, Ribeiro PH, Goldman GH, Nomizo A,

et. al .2008. Biological Activities from Extract of Endophytic Fungi isolated from Viguiera arenaria and Tithonia diversifolia. FEMS Immunol. Med. Microbiol.52 : 134-144

Guo BH., YC Wang, XW Zhou, K Hu, F Tan, ZQ Miao, KX Tang. 2006. An endophytic taxol-producing fungus BT2 isolated fromTaxus chinensis var. mairei.African. J. Biotech. 5 (10) : 875-877

Hajjaj H, Niederbeger P, Duboc P. 2001. Lovastatin biosynthesis by Aspergillus terreus in chemically defined medium. Appl. Envin. Microb. 67:2596-2602 Haque, ME., Pervin MM, Rahman MZ, Firdaus KMKB, Kabir MH, Rahman MA,

et al. 2005. Biological screening of some sewage microbes in Bangladesh. Asian J. Plant Sci. 4 (6) : 625-629

Harvey AL. 2008. Natural products in drug discovery. Drug Discov. Today 13 (19/20) : 894-901

Hasanah, M. 2005. Penelaahan terhadap plasma nutfah khusus: tanaman obat. [online].http://www.indoplasma.or.id/artikel/artikel_2005_penelaahan_pn_k husus_.html. Diakses 20 September 2006

Hayashi Y, Nishikawa Y, Mori H, Tamura H, Matsushita YI, Matsui T. 1998. Antitumor activity of (10E, 12Z)-9-hydroxy-10,12-octadecadienoic acid from rice bran.J. Ferment. Bioeng. 86 (2) : 149-153

Heo SH, Hou CT, Kim BS. 2009. Production of oxygenated fatty acids from vegetable oils by Flavobacterium sp strain DS5. New Biotechnol. 26 (1/2):105-108

Huang, WY., YZ Cai, KD Hyde, H Corke, M Sun. 2007. Endophytic fungi from Nerium oleander L (Apocynaceae): main constituents and antioxidant activity.World J Microbiol. Biotechnol.23:1253-1263

Husein AA, Bozzi B, Correa M, Capson TL, Kursar TA, Coley PD, Solis PN, Gupta MP. 2003. Bioactive constituents from three Vismia species.J. Nat. Prod. 66 : 858-860

Iwasaki Y, Brown W, Hou CT. 2002. Biosynthesis pathway of diepoxy bicyclic FA from linoleic acid byClavibactersp. ALA2.JAOCS. 79 (4) : 369-372

Jarvis, RM. dan R Goodecre. 2005. Genetic algorithm optimization for pre- processing and variable selection of spectroscopic data. Genet. Anal. 21 (7) : 860-868

Jasril, Lajis NH, Mooi LY, Abdullah MA, Sukari MA, Ali AM. 2003. Antitumor promoting and antioxidant activities of anthraquinones isolated from the cell suspension culture of Morinda elliptica. Asia Pacific J. Mol. Biol. Biotechnol. 11 ( 1) : 3-7

Jenni S, Leibundgut M, Maier T, Ban N. 2006. Architecture of fungal fatty acid synthase at 5 Å Resolution. Sci. 311: 1263-1267

Jiang L. 2010. Optimization of fermentation condition for pullulan production by Aureobasidium pullulan using response surface methodology.Carbohydrat Polym. 79 : 414-417

Kanwar AS. 2007. Brine shrimp (Artemia salina)-a marine animal for simple and rapid biological assays.J. Chinesse Clin. Med. 2 (4) : 236-240

Kennedy M, Krouse D. 1999. Strategies for improving fermentation medium performance: a review.J. Ind. Microb. Biotech. 23: 456-475

Khan A, Rahman M, Islam MS. 2008. Antibacterial, antifungal and cytotoxic activities of amblyone isolated fromAmorphophalus campanulatus. Indian. J. Pharmacol. 40 (1) : 41-44

Khan R, Shahzad A, Choudhary MI, Ahmad A. 2007. Biodiversity of The Endophytic Fungi Isolated from Calotropis procea (AIT) R.BR.Pak J Bot. 39 (6): 2233-2239

Khantamat O, Chaiwangyen W, Limtrakul P. 2004. Screening of flavonoid for their potential inhibitory effect on P-glycoprotein activity in human cervical carcinoma KB cells.Chiang Mai Med Bull. 43 (2):45-46

Klose J, Moniz de Sa M, Kronstad, JW. 2004. Lipid induced filamentous growth inUstilago maydis.Mol. Microbiol. 52: 823-835

Kock JLF, Strauss CJ, Pohl CH, Nigam S. 2003. The distribution of 3-hydroxy oxylipins in fungi.Prostag. Lip. Med. , 71, 85-96

Komiyama K, Funayama S. 1991. Antitumor Agent. Dalam : Omura, S (ed). The search for bioactive compounds from microorganism. New York. Springer- Verlag.

Kong JM, NK Goh, LS Chia, TP Chia. 2003. Recent advances in traditional plant drugs and orchids.Acta Pharmacol. Sin. 24 (1) : 7-21

Kumala S, Utji R, Sudarmono P, Kardono LBS. 2006. Isolation of endophytic fungi from Brucea javanica L (Merr) and cytotoxic evaluation of their n- butanol Extract from fermentation broth.Pakistan J Biolog. 9 (5): 825-832 Kuniyasu H. 2008. The roles of dietary PPAR gamma ligands for metastasis in

colorectal cancer. PPAR Research , 2008. [online]

doi:10.1155/2008/529720. Diakses tanggal 27 Mei 2011

Li, H., C Qing, Y. Zhang, Z. Zhao. 2005. Screening for endophytic fungi with antitumor and antifungal activities from chinese medicinal plants.World. J. Microbiol. Biotechnol. 21:1515-1519

Li, HJ., YC Lin, LLP Vrijmoed, EBG Jones. 2004. A new cytotoxic sterol produced by and endophytic fungus from Castaniopsis fissaat the South China Sea Coast.Chinese Chem.l Lett.15 (4) : 419-422

Li, HM., R Sullivan, M Moy, DY Kobayashi, FC Belanger. 2004. Expression of a novel chitinase by the fungal endophyte in Poa ampla. Mycologia. 96 (3) : 526-536

Li, Y., YC Song, JY Liu, YN Ma, RX Tan. 2005. Anti-Helicobacterpylori substances from endophytic fungal cultures. World. J. Microbiol. Biotech. 121: 553-558

Lin, J, X-J Yan, L Zheng, H-H Ma, H-M Chen. 2005. Cytotoxicity and apoptosis induction of some selected marine bacteria metabolites. J. Appl. Microbiol. 99 (6) : 1373-1382

Lin, X., C Lu, Y Huang, Z Zheng, W Su, Y Shen. 2007. Endophytic fungi from a pharmaceutical plant,Camptotheca acuminate: isolation, identification and bioactivity.World J. Microbiol. Biotechnol.23 : 1037-1040

Liu B, Timar J, Howlett J, Diglio CA, Honn KV.1991. Lipoxygenase metabolites of arrachidonic and linoleic acids modulate the adhesion of tumor cells to endhotelium via regulation of protein kinase C.Cell Regul. 2 : 1045-1055 Liu, JY., YC Song, Z Zhang, L Wang, ZJ Guo, WX Zou, RX Tan. 2004.

Aspergillus fumigatus CY018, an endophytic fungus in Cynadon dactylon as a versatile producer of new and bioactive metabolites.J.Biotechnol.114 : 279-287

Liu, X., M Dong, X Chen, M Jiang, X Lv, J Zhou. 2008. Antimicrobial activity of an endophytic fungiXylaria sp. YX-28 and identification of its antimicrobial compound 7-amino-4-methylcoumarin.Appl. Microbiol. Biotechnol.78:241- 247

Logrieco A, Moretti A, Fornelli F, Fogliano V, Ritieni A, Caiaffa MF, et al. 1996. Fusaproliferin production by Fusarium subglutinus and its toxicity to Artemia salina, SF-9 insect cells, and IARC/LCL 171 human B lymphocytes.Appl. Environ. Microbiol.62 (9) : 3378-3384

Maatooq GT, Marzouk AM, Gray AI, Rosazza JP. 2010. Bioactive microbial metabolites from glycyrrhetinic acid.Phytochem. 71 : 262-270

Macri F, Vianello A. 1976. Isolation and partial characterization of phytotoxins fromCurvularia lunata(Wakk.) Boed.Physiologl Plant Pathol, 8, 325-331 Magnani RF, Rodrigues-Fo E, Daolio C, Ferreira AG, de Souza AQL. 2003.

Three highly oxygenated coryophyllene sesquiterpene from Pestalotiopsis sp. a fungus isolated fromPinus taeda.Z. Naturforsch. 58C : 319-324 Mandenius CF, Brundin A. 2008. Bioprocess optimization using design of

experiment methodology.Biotechnol. Prog. 24: 1191-1203

Markaverich B, Mani S, Alejandro MA, Mitchell A, Markaverich D, Brown T,et al. 2002. A novel endocrine-disrupting agent in corn with mitogenic activity in human breast and prostatic cancer Cells. Environ. Health Perpect .110: 169-177

McLaughlin JL, Rogers LL, Anderson JE. 1998. The use of biological assays to evaluate the botanicals.Drug Inform. J. 12:19-25

Meot-Duros L, Cerantola S, Talarmin H, Meur CL, Floch GL, Magne C. 2010. New antibacterial and cytotoxic activities of falcarindiol isolated in Crithmum maritimumL. leaf extract.Food Chem. Toxicol.48 : 553-557 Meyer BN, Ferrigni NR, Putnam JE, Jacobsen LB, Nichols DE, McLaughlin JL.

1982. Brine Shrimp: A Convininet General Bioassay for Active Plant Constituents.J. Plant. Medic. 45 : 31-34

Mojica ERE, Micor JRL. 2007. Bioactivity of Barringtonia asiatica (Linnaeus) Kurz. seed aqueous extract inArtemia salina.Int. J. Bot. 3 (3) : 325-328 Moncheva P, Tishkov S, Dimitrova N, Chipeva V, Antonova-Nikolova S,

Bogatzevska N. 2002. Characteristics of soil actinomycetes from Antartica. J. Culture Collect. 3: 3-14

Montaher ABP, Pizzolati MG, Brighente IMK. 2002. An application of the brine shrimp bioassay for general screening of Brazilian medicinal plants. Acta Farm. Bonaerense21 (3): 175-17

Msikita W, Baimey H, James BD. 2007. Severity of Curvularia Stem Blight Disease of Cassava in West Africa .Plant disease , 91(11), 1430-1435 Mundova, MZ., K Drandarov, L Biglei, M Hesse, C Weines. 2002.

Biotransformation of 2-benzoxazolinone and 2-hydroxyl-4-benzoxazin-3- one by endophytic fungi isolated fromApelandra tetragona.Appl. Environt. Microbiol. 68 (10) : 4863-4870

Mundt S, Kreitlow S, Jansen R. 2003. Fatty acid with antibacterial activity from cyanobacterium Oscillatoria redekei HUB 051. J. Appl. Pshycol. 14:263- 267

Nelofer R, Syed Q, Nadeem M. 2008. Statistical optimization of process variables for L-lysine production by Corynebacterium glutamicum. Turk J Biochem. 33 (2) ; 50–57

Newman DJ, GM Craag, KM Snader. 2003. Natural product as sources of new drugs over the period 1981-2002.J. Nat. Prod. 66 : 1022-1037

Noverr M, Erb-Downward JR, Huffnagle GB. 2003. Production of eicosanoids and other oxylipins by pathogenic eukaryotic microbes. Clin. Microbiol. Rev. 16: 517-533

Oberlies, NH dan DJ Kroll. 2004. Campothecin and Taxol : Historic achievement in natural product research.J. Nat. Prod. 67: 129-135

Omar MN, Moynihan H, Hamilton R. 2003. Scaling-up production of 13S- hydroxy-9Z,11E—octadecadienoic acid (13S-HODE) through chemoenzymatic technique. Bull. Korean Chem. Soc. 24:397-399

Omura, S. 1986. Philosophy of new drug discovery. Mircob. Rev. 50 (3) : 259- 279

Ooijkaas LP, EC Wilkinson, J Tramper, RM Buitelaar. 1999. Medium optimization for spore production of Coniothyrium minitants using statiscally-based experimental design .Biotechnol. Bioeng. 64 (1): 93-100 Pal A, Ramana KV. 2009. Isolation and preliminary characterization of a

nonbacterial antimicrobial compound from Weissella paramesenteroides DFR-8 isolated from cucumber (Cucumis sativus). Proc. Biochem. 44 : 499-503

Pansuriya RC, Singhal RS. 2010. Response surface methodology for optimization of lovastatin by solid state fermentation. Brazilian. J. Microbiol. 41: 164-172

Parekh S, Vinci VA, Strobel RJ. 2000. Improvement of Microbial Strains and Fermentation Process. Appl. Microbiol. Biotech. 54 : 287-301

Petrini O, Sieber TN, Toti L, Viret O. 1999. Ecology, metabolite production and substrate utilization in endophytic fungi.Nat. Tox. 1 : 185- 196

Phongpaichit S, Nikom J, Rungjindamai N, Sakayaroj J, Hutadilok-Towatana N, Rukachaisirikul V, et al. 2007. Biological activities of extracts from endophytic fungi isolated from Garcinia plants. FEMS Immunol. Med. Microbiol. 51:517-525

Pisutthanan S, Plianbangchang P, Pisutthanan N, Ruanruay S, Muanrit O. 2004. Brine shrimp lethality activity of Thai medicinal plants in the family Meliaceae.Naresuan Univ.J.12 (2) : 13-18

Powers J-P S, Hancock REW. 2003. The relationship between peptide structure and antibacterial activity.Peptides24 : 1681 – 1691

Pramono E. 2002.The Commercial Use of Traditional Knowledge and Medicinal Plants in Indonesia. Multi Stake Holder Dialogue on Trade, Intelectual Property and Biological Resources in Asia. Brajendarapur: BRAC Center for Development Management

Prost I, Dhondt S, Rothe G, Vicente J, Rodriguez MJ, Kift N, et al. 2005. Evaluation of the antimicrobial activities of plant oxylipins supports their involvement in defence againts pathogens. Plant Physiol. 139 : 1902-1913 Puri SC, Nazir A, Chawla R, Arora R, Riyaz-ul-Hasan S, Amna T, et al. 2006.

The endophytic fungus Trametes hirsuta as a novel alternative source of podophyllotoxin and related aryl tetralin lignans. J. Biotechnol. 122 : 494- 510

Purwantiningsih, Hakim AR, Purwantini I. 2010. Antihyperuricemic activity of kepel Stelechocarpus burahol (Bl.) Hook. F. leaves extract and xanthine oxidase inhibitory study.Int. J. Pharm. Pharmaceut.Sci. 2 (2) : 123-127 Purwanto, Susilowati R. 2000. Hubungan struktur, ikatan kimia dan aktivitas

biologis obat. Didalam : Siswandono, Soekardjo B. Kimia Medisinal. Surabaya. Airlangga University Press.

Qin JC, Zhang YM, Gao JM, Bai MS, Yang SX, Laatsch H,et al.2009. Bioactive metabolite produced by Chaetomium globosum, and endophyticfungus isolated fromGingko biloba.Biorg. Medicin. Chem. Let.19 : 1572-1574 Quignard ELJ, Pohlit AM, Nunomura SM, da Silva Pinto AC, dos Santos EVM,

de Morais SKR, et al.2003. Screening of plants found in amazonas state for lethality toward brine shrimp.Acta Amaz. 33 (1) : 93-104

Radu S, Kqueen CY. 2002. Preliminary Screening of Endophytic Fungi from Medicinal Plants in Malaysia for Antimicrobial and Antitumor Activity.Malay J Med Sci. 9 (2) : 23-33

Raguse TL, Porter EA, Weisblum B, Gellman SH. 2002. Structure-activity studies of 14-helical antimicrobial β-peptides: Probing the relationship between conformational stability and antimicrobial potency. J.Am.Chem.Soc.124 : 12774-12785

Rawling BJ. 1998. Biosynthesis of fatty acids and related metabolites. Nat. Prod. Rep.: 275-307

Rhee S, Kitchener D, Brown T, Merrill R, Dilts R, Tighe S. 2004. Report in Biodiversity and Tropical Forest in Indonesia. Jakarta: USAID Indonesia Rombi M, Bordighera, 2002. Method for obtaining oil that is rich in

hydoxyoctadecadienoic fatty acids (HODE) or the esters thereof from a mixture containing linoleic acid or esters thereof.US Patent. 2002 Feb. 19. 6,348,609

Rondon MR, Goodman RM, Handelsman J. 1999. The Earth’s bounty: assessing and accessingsoil microbial diversity.TIBTECH17 : 403-409

Rosa LH, Machado KMG, Jacob CC, Capelari M, Rosa CA, Zani CL. 2003. Screening of Brazillian Basidiomycetes for antimcrobial activity. Mem Inst Oswaldo Crus98 (7) : 967-974

do Rosario Marinho AM, Rodrigues-Filho E, da Luz M, Morinho R, Santos LS. 2005. Biologically active polyketides produced by Penicillium janthinellum isolated as endophytic fungus from fruits of Melia azedarach. J. Braz. Chem. Soc.16 (2) : 280-283

Roubos JA, van Straten G, van Boxtel AJB. 1999. An Evolutionary Strategy for Fed-batch Bioreactor Optimization, Concepts and Performance. J.