Category Archives: PKS

Deconstructing aflatoxin biosynthesis

A paper in Science from Jason Crawford and colleagues explores the function of polyketide synthetases (PKS) in the synthesis of the secondary metabolite and carcinogen aflatoxin. Previous work (nicely reviewed in the fungi by Nancy Keller and colleagues) has shown the the PKS genes have several domains. These domains include acyl carrier protein (ACP), transacylase (SAT), ketosynthase (KS), malonyl-CoA:ACP transacylase (MAT), “product template” PT, Aand thioesterase/Claisen cyclase (TE/CLC).  These domains make up PksA, but the specific role of each domain’s in synthesis steps has not been fully worked out. Understanding this process and the specificity of the chemical structures that are created can help in redesign of these enzymes for synthesis of new molecules and drugs.

Then authors cloning and combining the domains from a cDNA template of pksA [accession AY371490]  (from Aspergillus parasiticus) into various combinations and then evaluated the synthesized products via HPLC.  This deconstruction of a complicated protein and its domains is a great example of functionally mapping the role of each part of the enzyme and integrating with the biochemistry of the synthesized products.  The findings of this research also mapped a role for the PT product template domain which could suggest where modifications could be made to tweak the synthesized products by these enzymes.

Crawford, J.M., Thomas, P.M., Scheerer, J.R., Vagstad, A.L., Kelleher, N.L., Townsend, C.A. (2008). Deconstruction of Iterative Multidomain Polyketide Synthase Function. Science, 320(5873), 243-246. DOI: 10.1126/science.1154711

Evolution of aflatoxin gene cluster


Blogging on Peer-Reviewed ResearchIgnazio Carbone and colleagues published a recent analysis of the evolution of the aflatoxin gene cluster in five Aspergillus fungi entitled “Gene duplication, modularity and adaptation in the evolution of the aflatoxin gene cluster” in BMC Evolutionary Biology. The authors were able to identify seven modules pairs of genes whose history of duplication were highly correlated. Several genomes of Aspergillus have been sequenced along with more Eurotioales fungi. Continue reading Evolution of aflatoxin gene cluster