An approach to the biosynthesis of the polyketide toxins excreted by the phytophagen fungus Botrytis cinerea

Botrytis cinerea is a well known pathogen of a number of commercial crops and produces many structurally diverse metabolites. There is no evidence for the production of host-specific toxins by this fungus, which is in accordance with the broad host range of this pathogen. Botrytis produces two series of phytotoxic metabolites: a family of characteristic sesquiterpene metabolites which contain the basic botryane skeleton, principally botrydial and dihydrobotrydial and two polyketide lactones types, botcinins and botrylactone [1,2,3]. The higher production of polyketide toxins from a botrydial sesquiterpene cyclase nock out mutant strain, led us to reinvestigate the structure and biosynthesis of these polyketide compounds.

Feeding experiments with ¹³C and ²H-labelled acetate and L-[methyl]methionine indicated that 3-acetylbotcineric acid is an acetate-derived polyketide whose methyl groups originate from L-[methyl]methionine. This is a rare example of the incorporation of a methyl from L-[methyl]methionine into a supposed C3 starter unit of the polyketide syntheses [4].

The similarity of botrylactone spectroscopic data with those of botcinins and the revision of stereochemistry reported for botrylactone indicated that both compounds have a common biosynthetic origin.

Here we propose to botrylactone as the biosynthetic precursor of botcinins toxins. So, B. cinerea biosynthesizes a C-20 polyketide which is methylated in activated methylene groups, followed by the loss of the starter–acetate unit.

References: 1. Tani, H. et al. (2005)J. Nat. Prod. 68: 1768–1772.

2. Tani, H. et al. (2006)J. Nat. Prod. 69: 722–72

3. Welmar, K. et al. (1979) Chem. Ber. 112: 3598–3602

4. Reino, J.L. et al. (2006)J. Org. Chem. 71: 562–565