Trapping Transient Protein–Protein Interactions in Polyketide Biosynthesis

Dissecting complex polyketide biosynthesis

Numerous bioactive natural products are synthesised by modular polyketide synthases. These compounds can be made in high yield by native multienzyme assembly lines. However, formation of analogues by genetically engineered systems is often considerably less efficient. Biochemical studies on intact polyketide synthase proteins have amassed a body of knowledge that is substantial but still incomp...

The stereochemistry of complex polyketide biosynthesis by modular polyketide synthases.

Polyketides are a diverse class of medically important natural products whose biosynthesis is catalysed by polyketide synthases (PKSs), in a fashion highly analogous to fatty acid biosynthesis. In modular PKSs, the polyketide chain is assembled by the successive condensation of activated carboxylic acid-derived units, where chain extension occurs with the intermediates remaining covalently boun...

Reactive Heterocycles for Examining Polyketide Biosynthesis

The biosynthesis of polyketide-derived mycotoxins.

The biosynthesis of a few representative polyketide-derived mycotoxins is reviewed: patulin, citrinin, diplosporin, ochratoxin A, maltoryzine, xanthomegnin, cytochalasans, ergochromes, zearalenone, citreoviridin, and the aflatoxins. Particular attention is given to the biosynthetic sequence: acetate----averufin----versiconal acetate----versicolorin A----sterigmatocystin----aflatoxin B1.

Polyketide biosynthesis: understanding and exploiting modularity.

Polyketide-based pharmaceuticals are some of our most important medicines. They are constructed in micro-organisms (typically bacteria and fungi) by gigantic enzyme catalysts called polyketide synthases (PKSs). The organization of PKSs into molecular assembly lines makes them particularly appealing targets for genetic engineering because, in principle, an alteration in the enzyme organization m...