Drug Discovery and Natural Products: End of an Era or an Endless Frontier?

被引：1549

作者：

Li, Jesse W. -H. ^{[1
]}

Vederas, John C. ^{[1
]}

机构：

[1] Univ Alberta, Dept Chem, Edmonton, AB T6G 2G2, Canada

来源：

SCIENCE | 2009年 / 325卷 / 5937期

基金：

加拿大自然科学与工程研究理事会;

关键词：

LEADS; MICROBIOLOGY; METAGENOMICS; DIVERSITY; CHEMISTRY; BIOLOGY;

D O I：

10.1126/science.1168243

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Historically, the majority of new drugs have been generated from natural products (secondary metabolites) and from compounds derived from natural products. During the past 15 years, pharmaceutical industry research into natural products has declined, in part because of an emphasis on high-throughput screening of synthetic libraries. Currently there is substantial decline in new drug approvals and impending loss of patent protection for important medicines. However, untapped biological resources, "smart screening" methods, robotic separation with structural analysis, metabolic engineering, and synthetic biology offer exciting technologies for new natural product drug discovery. Advances in rapid genetic sequencing, coupled with manipulation of biosynthetic pathways, may provide a vast resource for the future discovery of pharmaceutical agents.

引用

页码：161 / 165

页数：5

共 45 条

[1] Renaissance in antibacterial discovery from actinomycetes [J].

Baltz, Richard H. .

CURRENT OPINION IN PHARMACOLOGY, 2008, 8 (05) :557-563

[2] Metagenomics: Exploring unseen communities [J].

Blow, Nathan .

NATURE, 2008, 453 (7195) :687-692

[3] Marine natural products [J].

Blunt, John W. ;

Copp, Brent R. ;

Hu, Wan-Ping ;

Munro, Murray H. G. ;

Northcote, Peter T. ;

Prinsep, Michele R. .

NATURAL PRODUCT REPORTS, 2009, 26 (02) :170-244

[4] Improved Antifungal Polyene Macrolides via Engineering of the Nystatin Biosynthetic Genes in Streptomyces noursei [J].

Brautaset, Trygve ;

Sletta, Havard ;

Nedal, Aina ;

Borgos, Sven Even F. ;

Degnes, Kristin F. ;

Bakke, Ingrid ;

Volokhan, Olga ;

Sekurova, Olga N. ;

Treshalin, Ivan D. ;

Mirchink, Elena P. ;

Dikiy, Alexander ;

Ellingsen, Trond E. ;

Zotchev, Sergey B. .

CHEMISTRY & BIOLOGY, 2008, 15 (11) :1198-1206

[5]

*BRIST S COMP, 2004 GREEN SYNTH PAT

[6] Back to nature: Extinction of medicinal plants threatens drug discovery [J].

Brower, Vicki .

JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2008, 100 (12) :838-839

[7] Marine natural product libraries for high-throughput screening and rapid drug discovery [J].

Bugni, Tim S. ;

Richards, Burt ;

Bhoite, Leen ;

Cimbora, Daniel ;

Harper, Mary Kay ;

Ireland, Chris M. .

JOURNAL OF NATURAL PRODUCTS, 2008, 71 (06) :1095-1098

[8] The role of natural product chemistry in drug discovery [J].

Butler, MS .

JOURNAL OF NATURAL PRODUCTS, 2004, 67 (12) :2141-2153

[9] Structure-Activity Relationship Studies of the Two-Component Lantibiotic Haloduracin [J].

Cooper, Lisa E. ;

McClerren, Amanda L. ;

Chary, Anita ;

van der Donk, Wilfred A. .

CHEMISTRY & BIOLOGY, 2008, 15 (10) :1035-1045

[10] Real-Time DNA Sequencing from Single Polymerase Molecules [J].

Eid, John ;

Fehr, Adrian ;

Gray, Jeremy ;

Luong, Khai ;

Lyle, John ;

Otto, Geoff ;

Peluso, Paul ;

Rank, David ;

Baybayan, Primo ;

Bettman, Brad ;

Bibillo, Arkadiusz ;

Bjornson, Keith ;

Chaudhuri, Bidhan ;

Christians, Frederick ;

Cicero, Ronald ;

Clark, Sonya ;

Dalal, Ravindra ;

deWinter, Alex ;

Dixon, John ;

Foquet, Mathieu ;

Gaertner, Alfred ;

Hardenbol, Paul ;

Heiner, Cheryl ;

Hester, Kevin ;

Holden, David ;

Kearns, Gregory ;

Kong, Xiangxu ;

Kuse, Ronald ;

Lacroix, Yves ;

Lin, Steven ;

Lundquist, Paul ;

Ma, Congcong ;

Marks, Patrick ;

Maxham, Mark ;

Murphy, Devon ;

Park, Insil ;

Pham, Thang ;

Phillips, Michael ;

Roy, Joy ;

Sebra, Robert ;

Shen, Gene ;

Sorenson, Jon ;

Tomaney, Austin ;

Travers, Kevin ;

Trulson, Mark ;

Vieceli, John ;

Wegener, Jeffrey ;

Wu, Dawn ;

Yang, Alicia ;

Zaccarin, Denis .

SCIENCE, 2009, 323 (5910) :133-138

← 1 2 3 4 5 →