..Mr Tom Nicholson. Ph.D. Student 1996-1999.

Recent developments in the understanding of the molecular genetics of bacterial PKS systems (e.g. our own work on Type II PKS and the work of the Cambridge and USA groups with the modular PKS) have demonstrated that novel compounds can be developed by selective gene manipulation. Fungal polyketides are also of widespread pharmaceutical utility, and in fact are of widely diverging structural types. Very few fungal gene clusters for PKS enzymes have been discovered, in part because the bacterial PKS gene probes do not cross-hybridise well with fungal DNA. This project is developing independent gene probes specifically for fungal gene clusters using a PCR strategy. Current results show that the strategy is effective and a number of fungal gene clusters are under investigation. In parallel work, the expression of fungal gene clusters in bacterial systems is under active investigation. We, and others, have shown that the PKS gene for 6-methylsalicylic acid (6-MSA) is expressed in functional (presumably holo) form by Streptomyces species, and 6-MSA is produced. Our work is concentrating on the expression of newly cloned fungal PKS genes involved in the biosynthesis of unknown compounds. This strategy will offer a useful method for the manipulation of fungal genes as molecular genetic methods for fungi are poorly developed.