Navigation Links
Mining for gems in the fungal genome

Ever since penicillin, a byproduct of a fungal mold, was discovered in 1929, scientists have scrutinized fungi for other breakthrough drugs. As reported Jan. 20 in the Journal of Chemistry and Biology, a team led by a University of Wisconsin-Madison researcher has developed a new method that may speed the ongoing quest for medically useful compounds in fungi.

By manipulating a single fungal protein, the team, led by professor of plant pathology and medical microbiology Nancy Keller, pinpointed the genes responsible for creating dozens of secondary metabolites, a class of compounds that make good drug candidates. Already, analysis of one subset of these genes has revealed that they encode proteins required to produce an anti-tumor agent.

"We now have a new tool we can use to find secondary metabolites that are of pharmaceutical interest," says Keller. Although the team worked on a widely studied fungus, Aspergillus nidulans, the method can be used to find secondary metabolites in many other fungal species.

While primary metabolites are essential compounds that aid basic growth and reproduction in fungi, secondary metabolites are not required for life. "Secondary metabolites are bioactive compounds that are only produced at select times during the life cycle of the organism," explains Keller, noting that the compounds can help fungi survive various environmental stressors.

Some secondary metabolites have powerful heath effects in humans, such as penicillin, which certain fungi produce in the presence of bacteria. Fungi are also natural producers of antiviral agents, antifungals, other antibacterials, immunosuppressants and the popular cholesterol-lowering drug lovastatin.

Earlier methods to find secondary metabolites located just one compound at a time, and sometimes required prior knowledge about the compound of interest. Even after the genetic sequence of Aspergillus nidulans was completed in 2003, the search for secondary metabolites in that species continued. Although scientists were able to pinpoint the locations of genes believed to be involved in the production of secondary metabolites by pouring over the sequence data, the actual activity of the genes and their gene products still needed to be confirmed.

The method developed by Keller and her colleagues solves this problem and promises to broaden the search for medically useful agents by taking a powerful, genome-wide approach. Their technique is called "genomic mining" because of its robust ability to dig through an entire fungal genome to locate nearly all the hidden gems-the actively-produced secondary metabolites-at once.

The key to Keller's approach lies in a single fungal protein called LaeA. A few years ago, her team discovered that the presence of LaeA is required to turn on the genes that manufacture secondary metabolites in Aspergillus nidulans. "LaeA controls the production of secondary metabolites," says Keller.

For some as-yet unknown biological reason, all the genes required for the production of any given secondary metabolite-usually between three and two dozen genes-are located right next to each other along the chromosome in a gene cluster. These groups of genes stand out in certain scientific analyses, making secondary metabolite gene clusters easy to spot. Keller capitalized on these facts to find actively-produced secondary metabolites.

In one experiment, Jin Woo Bok, a research scientist in Keller's lab and co-author on the paper, deleted the LaeA gene in Aspergillus nidulans. Using a device called a microarray, the research team measured the activity of every gene in the LaeA-free mutant. "We looked at the entire 10,000 genes in this fungus," says Keller.

Keller's team searched the genome for groups of contiguous genes that were inactive in the mutant. They knew these were very likely to be gene clusters involved in the production of seco ndary metabolites.

In a parallel experiment, Bok designed a fungal strain that produced extra amounts of LaeA. This time, the team searched for groups of over-active genes, which they knew were likely secondary metabolite gene clusters.

The team's new approach located 40 active gene clusters; previously, fewer than ten secondary metabolites were known in this widely studied fungal species.

The newly discovered secondary metabolite gene clusters are already beginning to yield potentially useful medical agents. The team found an anti-tumor agent never before seen in Aspergillus nidulans. "It's just one of many [secondary metabolites to discover]," says Keller. "It's just the tip of the iceburg."

Thirty or so secondary metabolites await analysis in Aspergillus nidulans alone. Additionally, scientists suspect LaeA may play a similar role in all Aspergillus species, meaning there are over 180 fungi that can be mined using this technique. Keller also believes the mining strategy might work outside the Aspergillus genus with some modifications.

"This is really exciting," says Keller. "It's a method to find new metabolites, some of which we hope to be important ones."


'"/>

Source:University of Wisconsin-Madison


Related biology news :

1. Mining biotechs data mother lode
2. Light therapy may combat fungal infections, new evidence suggests
3. Symbiotic bacteria protect hunting wasps from fungal infestation
4. CO2 sensing proves critical for fungal pathogens to adapt to life in air and human hosts
5. Pillows - a hot bed of fungal spores
6. Genetic defenders protect crops from fungal disease
7. New method enables gene disruption in destructive fungal pathogen
8. U of M researchers discover genetic key to treating deadly fungal infections
9. Tearing down the fungal cell wall
10. Anti-fungal drug stops blood vessel growth
11. Antifungal drug kills TB bug
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:4/4/2017)... YORK , April 4, 2017   EyeLock ... today announced that the United States Patent and Trademark ... patent broadly covers the linking of an iris image ... same transaction) and represents the company,s 45 th ... latest patent is very timely given the multi-modal biometric ...
(Date:3/30/2017)... The research team of The Hong Kong Polytechnic University ... adopting ground breaking 3D fingerprint minutiae recovery and matching technology, pushing ... for use in identification, crime investigation, immigration control, security of access ... ... A research team led by Dr Ajay ...
(Date:3/28/2017)... 28, 2017 The report "Video ... Monitors, Servers, Storage Devices), Software (Video Analytics, VMS), and ... Global Forecast to 2022", published by MarketsandMarkets, the market ... is projected to reach USD 75.64 Billion by 2022, ... The base year considered for the study is 2016 ...
Breaking Biology News(10 mins):
(Date:10/11/2017)... ... October 11, 2017 , ... ... its endogenous context, enabling overexpression experiments and avoiding the use of exogenous expression ... guides is transformative for performing systematic gain-of-function studies. , This complement to ...
(Date:10/11/2017)... ... October 11, 2017 , ... ... it will be hosting a Webinar titled, “Pathology is going digital. Is your ... on digital pathology adoption best practices and how Proscia improves lab economics and ...
(Date:10/11/2017)... ... 2017 , ... Disappearing forests and increased emissions are the main causes of ... year. Especially those living in larger cities are affected by air pollution related diseases. ... most pollution-affected countries globally - decided to take action. , “I knew I had ...
(Date:10/10/2017)... SAN DIEGO, CALIF. (PRWEB) , ... October 10, 2017 , ... ... website as part of its corporate rebranding initiative announced today. The bold new ... broaden its reach, as the company moves into a significant growth period. , It ...
Breaking Biology Technology: