Stereochemistry of Polyketide Assembly in Fungi 13C, 2H and 3H Studies

Many of the above studies have given invaluable information on the stereochemical outcome of the ketoreductase and dehydratase catalysed reactions occurring during polyketide assembly in fungi. A number of studies of incorporation of [2H3]acetate have provided indirect information on the stereochemistry of the final enoyl reductase reaction. Thus 2H label is found at the pro- 

The stereochemistry of the ketosynthase-catalysed condensation of malona-te with the enzyme-bound thioester at the start of each elongation cycle has 

No discussion of studies on the stereochemical outcome of polyketide biosynthesis would be adequate without mention of the seminal studies of Jordan and Spencer [56-58] using chiral malonates to determine the stereospecificity of the elimination and enolisation reactions occurring during 6-MS A (66, R = H) and orsellinic acid (66, R = OH) biosynthesis. Early experiments by Abell and 

Staunton in which they compared the relative levels of 2H incorporation at the 3- and 5-positions from [2-2H3]- and [2-2HJacetates had already indicated that the loss of hydrogen was stereospecific, but were not able to define the stereochemistry [55]. 

A similar stereochemical outcome to that observed for 6-MSA was found using orsellinate synthase isolated from Penicillium cyclopium [58]. The hydrogens retained at C-3 and C-5 of orsellinic acid (66, R=OH) are from opposite prochiral sites in malonate. This contrasts with a previous study [59] on 

---