Fungal metabolite is an important source of natural products from which new pharmaceuticals can be developed. One such compound is the fungal secondary metabolite Squalestatin S1 isolated from the fungus Phoma species, which inhibits squalene synthase in the cholesterol biosynthetic pathway. Here the mechanisms of acyltransferases in the biosynthesis of Squalestatin S1 are investigated via in vitro enzyme assays with chemically modified substrates and intermediates. Preliminary results suggest that acyltransferase 1 (AT1) can acetylate the hydroxyl group at which the tetraketide chain attaches. However, it is unclear whether AT1 will accept both the unacetylated and the singly acetylated Squalestatin core as substrates.

Understanding fungal metabolism using chemically modified substrates

251st National Meeting (2016)

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