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Title: MODERN APPROACHES TO HARVESTING LICHEN PRODUCTS

Author
item MIAO, V - CUBIST PHARM, VANCOUVER
item LE GAL COEFFET, M - CUBIST PHARM, VANCOUVER
item Brown, Daren
item SINNEMANN, S - CUBIST PHARM, VANCOUVER
item DONALDSON, G - CUBIST PHARM, VANCOUVER
item DAVIES, J - CUBIST PHARM, VANCOUVER

Submitted to: Trends in Bio Techniques
Publication Type: Review Article
Publication Acceptance Date: 9/1/2001
Publication Date: N/A
Citation: N/A

Interpretive Summary: Lichens are a composite of organisms representing three kingdoms: fungi, green algae and cyanobacteria. Lichens and lichen products have held a place in traditional medicines for centuries and serve as alternative treatments in various parts of the world today. Modern drug discovery efforts have shied away from lichens due to their slow growing nature. The need for new natural product drugs increases daily as previously reliable standard drugs become less effective against new strains of multidrug-resistant pathogens. An alternative approach to access the biosynthetic potential of lichens is to clone lichen DNA and express biosynthetic pathway genes in well characterized surrogate hosts. Sequencing and structural analysis of cloned lichen DNA revealed that polyketide biosynthetic genes are clustered and that lichens contain a rich source genetic/biosynthetic potential. Preliminary studies using Aspergillus nidulans as a potential host for heterologous expression system indicate that it is able to recognize some lichen promoters and correctly splice out introns in lichen genes. Future studies are directed at developing heterologous promoter systems and further refining host-expression system.

Technical Abstract: Lichens are a composite of organisms representing three kingdoms: fungi, green algae and cyanobacteria. There are over 13,500 described species, including almost one fifth of all know fungi. Lichens and lichen products have held a place in traditional medicines for centuries and serve as alternative treatments in various parts of the world today. Modern approaches to discovering novel pharmaceutical products have ignored lichens due primarily to their slow growing nature. Recent molecular genetic approaches provide the means to directly access lichen genomes to reveal and eventually harvest their potential for production of novel secondary metabolites. Sequencing and structural analysis of cloned lichen DNA revealed that polyketide biosynthetic genes are clustered, and that cyanobacterial photobionts also contribute to the biosynthetic pathways that can be captured in phage and cosmid libraries. Preliminary studies using Aspergillus nidulans as a potential host for heterologous expression system indicate that it is able to recognize some lichen promoters and correctly splice out introns in lichen genes. The cloning and expression of biosynthetic pathway genes into well characterized surrogate hosts will permit rapid identification of novel products and the DNA fragments responsible for their synthesis. This provides a new approach to the discovery of low molecular weight biologicals.