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

EMBO workshop on Evolutionary and Environmental Genomics of Yeasts

I got this announcement this in the mail

EMBO Workshop on Evolutionary and Environmental Genomics of Yeasts 

taking place at

EMBL Heidelberg, 1-5 October 2008
Please register online at
Registration deadline is August 1st – only online applications accepted!

More information can be found at

Phytophthora work highlighted

A link to the story about Matteo Garbelotto‘s work on Phytophthora ramorum and showing that the source in California is likely from ornamentals from a nursery. The work is to appear soon in Molecular Ecology but alas is not available yet.

A recent paper on updated Phytophthora phylogeny from Jamie Blair and co-authors is also out in FGB. They used genome sequences to determine additional markers for multi-locus sequencing and then sequenced and built trees from 82 taxa. 

Server changes

LogoThe old site I setup during my PhD (fungal.genome.duke.edu) was shutdown by Duke. I have been able to migrate the domain name to the fungalgenome.org site that is funded by the TaylorLab, but have not had time to restore all functionality of the old data and site.

In the future I hope the community will consider what are important resources to utilizing these genomic data and how we want to fund and see these types of resources perpetuated.

Summer 2008, Mycological Meetings

A few of the summer meetings that relate to fungal biology and evolution. 

Hope to see you at some of these.

Coprinus on the heart?

Here’s a fungal infection you don’t hear much about. One of the fungi we work on, a model for mushroom development as it can be fruited in the lab is Coprinopsis cinerea (previously named Coprinus cinereus). C. cinerea is a saprobric coprophillic fungus so it is usually found on dung.  Although rare in human infections there are a few reports in immunocopromised patients.  Below is an abstract describing isolation of C. cinerea from an implanted heart valve from a pig. This definitely not its typical habitat and Coprinus growing in yeast form I’m sure I’ve really heard of either.  Would be great to see if the clinical strains are still sexually competent and/or are significantly different in other ways (growth rate, resistance to drugs and oxidative stress) from the wild or laboratory strains.

A 77-year-old female initially presented with symptomatic mitral valve stenosis involving a bioprosthesis that had been implanted 8 months earlier for myxomatous mitral valve disease and severe valvular regurgitation. The patient was taken for a second mitral valve replacement due to stenosis. Intraoperatively, the bioprosthetic mitral valve was noted to have an unusual clot-like mass on the atrial side. Initial fungal smears were positive for yeast stains, and pathology revealed extensive colonization by thick filamentous fungus with apparent true hyphae, pseudohyphae, and yeast forms. The fungus was identified as Hormographiella aspergillata, the asexual form of Coprinus cinereus, a common inky cap mushroom that grows in the lawn.

Continue reading Coprinus on the heart?

Lest you think annotation is easy

Ensembl!Ewan Birney and Ensembl (the other/original genome browser depending on if you are a UCSC junkie) have started blogging a bit more about what is going on under the proverbial hood over there in Hinxton.  There are some great nuggets talking about what are some of the current problems.  These bite-sized comments should be a great glimpse into what is going on without drowning in the deluge that is ensembl-dev.  

This is a recent post on the challenges of gene annotation coordination among “manual” and “automated” annotation of gene structure of groups at the same institution.  

Scale that up among multiple genomes, genome centers, quality of prediction programs and assemblies, and you can see why the fungal genome comparisons could use a little bit more help. It is great to hear what the animal genome annotation groups are doing to solve informatics challenges and data management issues and coordination. I’m big fan of more informatics+science in the open where it is feasible.