Monthly Archives: February 2014

So, What Can You Do with a “Natural Product”?

In case you haven’t noticed, there is a lot of work going on to discover useful, new natural compounds from nature. There is a long list of possibilities. We’re most interested in biologically active molecules from soil organisms- Burkholderia sp. to be more specific.

Burkholderia (formerly known as Pseudomonas) are a diverse genus of soil microorganisms responsible for a wide variety of biological substances. When bacteria live in the soil, some develop “predator” tendencies capable of clearing a path for themselves by secreting various chemical substances. These can be substances to create a beneficial (symbiotic) relationship with plants to improve growth or, can be fatal to competitive microorganisms. It depends on what is best for the Burkholderia’s survival.

With the groundbreaking work of Dr. Joseph O. Falkingham III of Virginia Tech’s Department of Biological Sciences, molecules produced by a species of Burkholderia  have been isolated and characterized. These molecules, called burkholdines are cyclic peptides that have very important anti-fungal properties. These burkholdines are produced in small quantities but, they are very powerful. Compared to one of the first antiifungal drugs from the 1950’s, Amphotericin B, they are 25 times more powerful.

This anti-fungal drug and others are still in use today. The problem is many have big side effects and cannot be taken for long periods of time. In some cases, the drug kills the patient before the infection does.

Work in Dr. Falkingham’s lab and his collaborators has been able to determine the chemical structure of three of these cyclic peptides but, there are perhaps a half dozen more of these elusive compounds remaining to be discovered.

Example of a Burkholdine Molecule

Example of a Burkholdine Molecule

This molecule would be impossible to create synthetically in the laboratory or, would be impossibly expensive to do so, why not let nature do it?

There is a renaissance in Molecular Biology and Combinatorial Chemistry to manufacture these compounds with genetic engineering techniques. It has been done with insulin for diabetes, Tissue Plasminogen Activatory to stop heart attacks and even Lovostatin to lower Cholesterol.

Before this technology was available, pig pancreases were used to produce insulin, human placentas were used to produce human growth hormone and Interferon was produced in tissue culture. That has all now changed to allow bacteria to act as “factories” with the natural machinery to do what man cannot.

Our journey begins with what can we produce with these weird looking molecules. They can prevent mold on your strawberries but, someday they may treat Athlete’s foot or, chronic lung infections for transplant, AIDS or TB patients! So, that’s what you can do with natural products! Don’t get me started on what the cost of commercialization will be for something like that………

Here are some Journal Articles if you would like to read more:

Cain, C.C., A.T. Henry, R.H. Waldo, III, L.J. Casida, Jr., and J.O. Falkinham, III. 2000. Identification and characteristics of a novel Burkholderia strain with broad-spectrum antimicrobial activity. Appl. Environ. Microbiol. 66:4139-4141.

Clardy, Jon, Fishbach, Michael A., Walsh, C.T., 2006. New antibiotics from bacterial natural products. Nature Biotechnology 24:12:1541-1550

De Groot, M. A., N. R. Pace, K. Fulton, and J. O. Falkinham, III. 2006. Relationships between Mycobacterium isolates from patients with pulmonary mycobacterial infection and potting soils. Appl. Environ. Microbiol. 72:7062-7606.

Gu, G., Smith, L. Liu, A.I. and Lu, S.E.. 2011. Genetic and Biochemical Map for the Biosynthesis of Occidiofungin, an Antifungal Produced by Burkholderia contaminans Strain MS14. Appl. Environ. Microbiol. 77: 6189-6198.

Lin, Z., J.O. Falkinham, III, K.A. Tawfik, P. Jeffs, B. Bray, G. Dubay, J.E. Cox,E. W. Schmidt. 2012. Burkholdines from Burkholderia ambifaria: antifungal agents and possible virulence factors. J. Nat. Prod. 75: 1518-1523.

Tawfik, K.L., P. Jeffs, B. Bray, G. Dubay, J.O. Falkinham, III, M. Mesbah, D. Youssef, S. Khalifa, and E.W. Schmidt. 2009. Burkholdines 1097 and 1229, potent antifungal peptides form Burkholderia ambifaria 2.2 N. Organic Letters 12: 664-666.

Walsh, C.T Combinatorial biosynthesis of antibiotics: challenges and opportunities. Chem. Bio Chem. 3,125-134 (2002)