Antitumor polyketide biosynthesis by an uncultivated bacterial symbiont of the marine sponge Theonella swinhoei

Proceedings of the National Academy of Sciences of the United States of America - Tập 101 Số 46 - Trang 16222-16227 - 2004
Jörn Piel1, Dequan Hui1, Gaiping Wen1, Daniel Butzke1, Matthias Platzer1, Nobuhiro Fusetani1, Shigeki Matsunaga1
1Department of Bioorganic Chemistry, Max Planck Institute for Chemical Ecology, Hans-Knöll-Strasse 8, Beutenberg Campus, 07745 Jena, Germany; Genome Analysis, Institute of Molecular Biotechnology, Beutenbergstrasse 11, Beutenberg Campus, 07745 Jena, Germany; and Graduate School of Agricultural and Life Sciences, University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan

Tóm tắt

Bacterial symbionts have long been suspected to be the true producers of many drug candidates isolated from marine invertebrates. Sponges, the most important marine source of biologically active natural products, have been frequently hypothesized to contain compounds of bacterial origin. This symbiont hypothesis, however, remained unproven because of a general inability to cultivate the suspected producers. However, we have recently identified an uncultured Pseudomonas sp. symbiont as the most likely producer of the defensive antitumor polyketide pederin in Paederus fuscipes beetles by cloning the putative biosynthesis genes. Here we report closely related genes isolated from the highly complex metagenome of the marine sponge Theonella swinhoei , which is the source of the onnamides and theopederins, a group of polyketides that structurally resemble pederin. Sequence features of the isolated genes clearly indicate that it belongs to a prokaryotic genome and should be responsible for the biosynthesis of almost the entire portion of the polyketide structure that is correlated with antitumor activity. Besides providing further proof for the role of the related beetle symbiont-derived genes, these findings raise intriguing ecological and evolutionary questions and have important general implications for the sustainable production of otherwise inaccessible marine drugs by using biotechnological strategies.

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Tài liệu tham khảo

10.1039/b310175b

10.1039/a909113k

10.1007/s001140100211

10.1517/13543784.12.8.1367

10.1007/s002270000273

10.1351/pac199466101983

10.1007/s101260000026

10.1128/AEM.67.10.4531-4537.2001

10.1073/pnas.222481399

10.1007/BF00328445

10.1002/cbic.200300782

10.1128/JB.186.5.1280-1286.2004

10.1039/b100191o

10.1002/(SICI)1521-3773(19980904)37:16<2162::AID-ANIE2162>3.0.CO;2-2

10.1021/ol049503q

10.1021/jm030207d

10.1016/0040-4020(95)00405-W

10.1111/j.1462-2920.2004.00531.x

10.1021/cr00021a007

10.1016/S1367-5931(03)00016-4

10.1128/AEM.68.9.4431-4440.2002

10.1111/j.1432-1033.1989.tb15056.x

10.1016/S1074-5521(03)00091-7

10.2174/1385272033486648

10.1073/pnas.222228199

10.1002/(SICI)1521-1878(199806)20:6<480::AID-BIES6>3.0.CO;2-Q

10.1128/MCB.21.4.1111-1120.2001

10.1128/AEM.70.6.3724-3732.2004

10.1021/ja00025a054

10.1016/S1074-5521(99)80082-9

10.1016/S1074-5521(00)00011-9

10.1038/35000624

10.1099/00221287-145-11-3059

10.1073/pnas.0537286100

10.1016/j.chembiol.2004.03.030

Pavan, M. & Bo, G. (1953) Physiol. Comp. Oecol. 3, 307-312.

Narquizian, R. & Kocienski, P. J. (2000) in The Role of Natural Products in Drug Discovery, eds. Mulzer, R. & Bohlmann, R. (Springer, Heidelberg), Vol. 32, pp. 25-56.

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Proceedings of the National Academy of Sciences of the United States of America

Tập 101 Số 46

16222-16227

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