Corante

About this Author
DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

Chemistry and Drug Data: Drugbank
Emolecules
ChemSpider
Chempedia Lab
Synthetic Pages
Organic Chemistry Portal
PubChem
Not Voodoo
DailyMed
Druglib
Clinicaltrials.gov

Chemistry and Pharma Blogs:
Org Prep Daily
The Haystack
Kilomentor
A New Merck, Reviewed
Liberal Arts Chemistry
Electron Pusher
All Things Metathesis
C&E News Blogs
Chemiotics II
Chemical Space
Noel O'Blog
In Vivo Blog
Terra Sigilatta
BBSRC/Douglas Kell
ChemBark
Realizations in Biostatistics
Chemjobber
Pharmalot
ChemSpider Blog
Pharmagossip
Med-Chemist
Organic Chem - Education & Industry
Pharma Strategy Blog
No Name No Slogan
Practical Fragments
SimBioSys
The Curious Wavefunction
Natural Product Man
Fragment Literature
Chemistry World Blog
Synthetic Nature
Chemistry Blog
Synthesizing Ideas
Business|Bytes|Genes|Molecules
Eye on FDA
Chemical Forums
Depth-First
Symyx Blog
Sceptical Chymist
Lamentations on Chemistry
Computational Organic Chemistry
Mining Drugs
Henry Rzepa


Science Blogs and News:
Bad Science
The Loom
Uncertain Principles
Fierce Biotech
Blogs for Industry
Omics! Omics!
Young Female Scientist
Notional Slurry
Nobel Intent
SciTech Daily
Science Blog
FuturePundit
Aetiology
Gene Expression (I)
Gene Expression (II)
Sciencebase
Pharyngula
Adventures in Ethics and Science
Transterrestrial Musings
Slashdot Science
Cosmic Variance
Biology News Net


Medical Blogs
DB's Medical Rants
Science-Based Medicine
GruntDoc
Respectful Insolence
Diabetes Mine


Economics and Business
Marginal Revolution
The Volokh Conspiracy
Knowledge Problem


Politics / Current Events
Virginia Postrel
Instapundit
Belmont Club
Mickey Kaus


Belles Lettres
Uncouth Reflections
Arts and Letters Daily
In the Pipeline: Don't miss Derek Lowe's excellent commentary on drug discovery and the pharma industry in general at In the Pipeline

In the Pipeline

« Bernard Munos on The Last Twelve Years of Pharma | Main | New Photos, Same Blather »

June 18, 2013

Forcing Fungi to Make Stranger Compounds

Email This Entry

Posted by Derek

Natural products come up around here fairly often, as sources of chemical diversity and inspiration. Here's a paper that combines them with another topic (epigenetics) that's been popular around here as well, even if there's some disagreement about what the word means.

A group of Japanese researchers were looking at the natural products derived from a fungus (Chaetomium indicum). Recent work has suggested that fungi have a lot more genes/enzymes available to make such things than are commonly expressed, so in this work, the team fed the fungus an HDAC inhibitor to kick its expression profile around a bit. The paper has a few references to other examples of this technique, and it worked again here - they got a significantly larger amount of polyketide products out of the fermentation, included several that had never been described before.

There have been many attempts to rejigger the synthetic machinery in natural-product-producing organisms, ranging from changing their diet of starting materials, adding environmental stresses to their culture, all the way to manipulating their actual
genomic sequences directly. This method has the advantage of being easier than most, and the number of potential gene-expression-changing compounds is large. Histone deacetylase inhibitors alone have wide ranges of selectivity against members of the class, and then you have the reverse mechanism (histone actyltranferase), methyltransferase and demethylase inhibitors, and many more. These should be sufficient to produce weirdo compounds a-plenty.

Comments (4) + TrackBacks (0) | Category: Chemical Biology | Natural Products


COMMENTS

1. paperclip on June 18, 2013 1:03 PM writes...

This really is fascinating stuff. Time and again it is seen that fungi in the lab produce just a fraction of the compounds that their genomes suggest they are capable of making. The next great antibiotic could be locked away in one of those fungi. HDAC inhibitors seem to pry out a couple more compounds sometimes, but not everything. Although researchers are trying to find out the rhyme and reason to it all, for now the best thing is to try anything you can think of to induce a fungus to produce more.

Permalink to Comment

2. Anonymous on June 18, 2013 6:54 PM writes...

Thanks for the updated picture!

I love how your color changes with the surroundings - are you sure you're not part chameleon?

And thanks for blogging so prolifically - it's always interesting to read!

Permalink to Comment

3. simpl on June 19, 2013 10:05 AM writes...

How far off is a yeast-based production of atorvastatin?

Permalink to Comment

4. Aspergil on June 20, 2013 9:16 AM writes...

I'm a fungal molecular biologist that works on secondary metabolites. As you state, there are several studies that use this chemical induction approach to get fungi to express many of their normally silent secondary metabolite genes. Now that we have genome sequences for many fungi, we can see that there are far more secondary metabolite genes than there are defined products. People in the field have been going after these genes with promoter replacements and heterologous expression hosts. This work is rapidly accelerating compound discovery and will only get faster in the future. I would argue that yeast-based production is not as efficient as production in filamentous fungi. Genetic manipulation in filamentous fungi is far more advanced than most people are aware of. There is very little difference in genetic manipulation of yeasts and filamentous fungi.

Permalink to Comment

POST A COMMENT




Remember Me?



EMAIL THIS ENTRY TO A FRIEND

Email this entry to:

Your email address:

Message (optional):




RELATED ENTRIES
One and Done
The Latest Protein-Protein Compounds
Professor Fukuyama's Solvent Peaks
Novartis Gets Out of RNAi
Total Synthesis in Flow
Sweet Reason Lands On Its Face
More on the Science Chemogenomic Signatures Paper
Biology Maybe Right, Chemistry Ridiculously Wrong