Your browser version may not work well with NCBI's Web applications. More information here...
1: Nat Biotechnol. 2003 Feb;21(2):187-90. Epub 2003 Jan 21.
Related Articles, Links
Click here to read Click here to read
A genomics-guided approach for discovering and expressing cryptic metabolic pathways.

Zazopoulos E, Huang K, Staffa A, Liu W, Bachmann BO, Nonaka K, Ahlert J, Thorson JS, Shen B, Farnet CM.

Ecopia BioSciences, Inc., 7290 Frederick Banting, Montreal, Quebec H4S 2A1, Canada.

Genome analysis of actinomycetes has revealed the presence of numerous cryptic gene clusters encoding putative natural products. These loci remain dormant until appropriate chemical or physical signals induce their expression. Here we demonstrate the use of a high-throughput genome scanning method to detect and analyze gene clusters involved in natural-product biosynthesis. This method was applied to uncover biosynthetic pathways encoding enediyne antitumor antibiotics in a variety of actinomycetes. Comparative analysis of five biosynthetic loci representative of the major structural classes of enediynes reveals the presence of a conserved cassette of five genes that includes a novel family of polyketide synthase (PKS). The enediyne PKS (PKSE) is proposed to be involved in the formation of the highly reactive chromophore ring structure (or "warhead") found in all enediynes. Genome scanning analysis indicates that the enediyne warhead cassette is widely dispersed among actinomycetes. We show that selective growth conditions can induce the expression of these loci, suggesting that the range of enediyne natural products may be much greater than previously thought. This technology can be used to increase the scope and diversity of natural-product discovery.

Publication Types:
PMID: 12536216 [PubMed - indexed for MEDLINE]