Actinobacteria: the good, the bad, and the ugly
- 901 Downloads
The actinobacteria are arguably the richest source of small molecule diversity on the planet. These compounds have an incredible variety of chemical structures and biological activities (in nature and in the laboratory). Their potential for the development of therapeutic applications cannot be underestimated. It is suggested that an improved understanding of the biological roles of low molecular weight compounds in nature will lead to the discovery an inexhaustible supply of novel therapeutic agents in the next decade. To support this objective, a functional marriage of biochemistry, genomics, genetics, microbiology, and modern natural product chemistry will be essential.
KeywordsAntibiotics Bioactive molecules Chemical diversity Genomics Molecular evolution Natural products Signaling Therapeutics
We are grateful to Dorothy Davies for her patient editing assistance and Dr. Marco Ventura for permission to reproduce Fig. 1. Funding has been provided by the National Science and Engineering Research Council, the Canadian Institutes for Health Research, Merck Research Laboratories, and the Tally Fund.
- Demain AL, Sanchez S (2009) Microbial drug discovery: 80 years of progress. J Antibiot (Tokyo) 62:5–16Google Scholar
- Hershkovitz I, Donoghue HD, Minnikin DE, Besra GS, Lee OY, Gernaey AM, Galili E, Eshed V, Greenblatt CL, Lemma E, Bar-Gal GK, Spigelman M (2008) Detection and molecular characterization of 9000-year-old Mycobacterium tuberculosis from a neolithic settlement in the eastern Mediterranean. PLos One 3:e3426CrossRefPubMedGoogle Scholar
- Kaufman SHE, van Helden P (2008) Handbook of tuberculosis vol. 3: clinics, diagnostics, therapy and epidemiology. Wiley-VCH, WeinheimGoogle Scholar
- McLeod MP, Warren RL, Hsiao WW, Araki N, Myhre M, Fernandes C, Miyazawa D, Wong W, Lillquist AL, Wang D, Dosanjh M, Hara H, Petrescu A, Morin RD, Yang G, Stott JM, Schein JE, Shin H, Smailus D, Siddiqui AS, Marra MA, Jones SJM, Holt R, Brinkman FSL, Miyauchi K, Fukuda M, Davies JE, Mohn WW, Eltis LD (2006) The complete genome of Rhodococcus sp. RHA1 provides insights into a catabolic powerhouse. Proc Natl Acad Sci USA 103:15582–15587CrossRefPubMedGoogle Scholar
- Putze J, Hennequin C, Nougayrède J-P, Zhang W, Homburg S, Karch H, Bringer M-A, Fayolle C, Carniel E, Rabsch W, Oelschlaeger TA, Oswald E, Forestier C, Hacker J, Dobrindt U (2009) Genetic structure and distribution of the colibactin genomic island among members of the family Enterobacteriaceae. Infect Immun 77:4696–4703CrossRefPubMedGoogle Scholar
- Taylor RF (1984) Bacterial triterpenoids. Microbiol Mol Biol Rev 48:181–198Google Scholar
- Van der Geize R, Yam K, Heuser T, Wilbrink MH, Hara H, Anderton MC, Sim S, Dijkhuizen L, Davies JE, Mohn WH, Eltis LE (2007) A gene cluster encoding cholesterol catabolism in a soil actinomycete provides insight into Mycobacterium tuberculosis survival in macrophages. Proc Natl Acad Sci USA 104:1947–1952CrossRefPubMedGoogle Scholar
- Winans SC, Bassler BL (eds) (2008) Chemical communication among bacteria. ASM Press, Washington, DCGoogle Scholar