Author Archives: Leone BioVentures,LLC

About Leone BioVentures,LLC

I am the President of American Biosystems,Inc. and our new subsidiary, Leone BioVentures,LLC. We hope to "Change the World" through more economical and effective bio control products.

Fungal Diseases of Oil Palms

Basal Stem Rot (BSR) in Oil Palms- Do we have a solution?

We have recently learned that Basal Stem Rot is a problem in Oil Palms. If you are involved in the study of this disease or, interested in working on a possible biological solution to the problem, we would like to hear from you.

basal-stem-rot-in-oil-palms

Ganoderma boil-palmininense is affecting an important source of commerce in Asia. Read about the threat here:

Plantwise KnowledgeBank

 

Progress is measured in inches, not miles!

We are continuing to improve yield and functionality of our lead compounds. With the intent on learning more about the bio-pesticide marketplace, we will again we attending the Informa Bio-pesticide forum in Raleigh in July and the Ag Showcase in September this year. We continue to look for partners for development of these exciting compounds for either therapeutic or bio-pesticide applications.

Our burkholdine compounds are being tested for activity against a variety of Cryptococcus  species responsible for the death of 60,000 people worldwide per year. At the other end of the spectrum, we are working with the USDA to test our compounds to fight the fungus attacking ‘Ōhi’a trees in Hawaii. Over 34,000 acres of the total 865,000 acres of these indigeneous trees are affected.

See http://www.npr.org/2016/04/07/473384008/rapid-hia-death-the-disease-thats-killing-native-hawaiian-trees

Scientists say five years ago, this was a lush, green native forest. But a deadly fungus is killing thousands of 'ōhi'a trees. This is the Big Island, where researchers believe the disease first took hold.

Link

Edward Goyette, CEO and/or Larissa Smith, CSO will be attending the following events in 2015. Please give us a call to learn more about our progress!

Ag Biotech Entrepreneurial Showcase 2015, Raleigh, NC May, 19,2015

http://www.ncbiotech.org/AgBiotechShowcase

Informa Life Science Crops & Chemicals USA, Raleigh,NC July 22-23,2015

http://www.informa-ls.com/event/cropsandchemicalsusa

Ag Innovation Showcase, St. Louis, MO, September 14-16,2015

http://www.agshowcase.com/

BPIA Fall Semi-Annual Meeting and Registration Workshop. Washington,DC: September 16th-18th      BPIA meeting details

We hope to see you at these top- notch events!

EPA Registration

In the past few weeks, we engaged the US Environmental Protection Agency in order to determine a path for  registration for our product as a biochemical pesticide. The meeting went well and we have been presented with a reasonably cost effective path to registration. Bio-pesticides enjoy a more simplified and cost effective registration procedure than conventional pesticides because of their natural product nature in the environment. If a chemical compound has been existing in nature for thousands of years and, has not caused any particular problems in the environment, it probably will not cause problems in the future. There is still a substantial amount of toxicology, safety and stability data required of any product used even in soil applications and greenhouses. Such testings includes honeybees, ladybugs and other animals possibly exposed to the compounds.

As an example, Bacillus thuringensis was first approved for use as a bio-pesticide in the early 1900’s and is still in use today. We hope to be able to offer the same level of effectiveness and safety as this and other bio-pesticides on the market today.

New Field Testing Program to Begin in May 2014

We have been very fortunate to complete 72 field tests over the past 15 years with our Leone Bio-fungicide. Next month, we are pursuing 4 new field trials with Corn, Cotton, Soybeans and Peanuts. These are all important agricultural crops for the state of Virginia as well as many agricultural producing regions around the world.

The field tests will be taking place at the Virginia Tech Agricultural Research Station in Suffolk, Virginia and, are conducted by Dr. Hillary Mehl. We are thrilled to be working with Hillary as she has previous bio-pesticide development experience and is a graduate of University of California-Davis (the hotbed of bio-pesticide research).

Hillary will be looking at the opportunity for Leone to reduce nematode infestation.We will also be looking for an overall improvement in crop yield by reducing soil fungi that negatively affect seed germination and plant growth.

With the world’s food requirements increasing drastically over the next 30 years, any improvement in crop yields via natural products friendly to the environment will be sorely needed. We hope to offer one such solution!

Results are expected this fall with toxicology studies to commence this fall. Stay tuned!

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)

Testing, Testing, Testing!

There was an interesting post in AG Professional entitled “The rise of Biologicals”. As one might expect, there is interest in using environmentally safe and friendly pesticides instead of conventional chemicals. My father spent 30 years in the conventional pesticide business and always felt that  after Since Silent Spring pesticides were always going to be given a bad rap.

When you live in a country where the majority of people are only concerned with the quality of their food and can’t imagine worrying about the presence of it, it is easy to understand. With demands on the world’s food supply to double over the next 35 years, existence of food will begin to take on a new urgency.

So, what have we to offer with biological pesticides? In some cases, conventional pesticides simply do not do the job. I attended the tobacco workers conference in Pinehurst, North Carolina last week and many crops have disease problems without solutions. I spoke with a representative from Valent Crop Sciences about their new Presidio(tm) fungicide for tobacco. Tobacco has a number of disease problems Black Shank, Leaf spot and others which are still not completely under control. The new Valent product looks promising but, disease resistance, workers safety and the environmental consequences will always remain.

Nobody eats tobacco but, it is still an important cash crop in the eastern US and high-tech companies are utilizing it for production of pharmaceuticals so, we have heard the last from this ancient crop.

There was a presentation from an organic farmer that has been producing up to 160 acres of tobacco for almost 15 years and, the economics of organic production make sense. He can make more money (almost twice in some cases) with organic production. He has to jump through some hoops to qualify but, he is being greatly rewarded for his skill in this regard.

We are now trying to find a place to start with our Leone bio-fungicide at this moment. Where should we start? Many crops have disease problems which result in crop loses of up to 20% worldwide because of fungus infestations. Yes, things like bananas, apples, corn, wheat, rice and peanuts.

Since we are trying to find the most economical path to commercialization, the crop of choice may not be a popular fruit or vegetable. It may not even be a fruit or vegetable consumed for food! The reason is the EPA makes it easier to apply for registration for crops that really don’t provide food but, do use lots of conventional pesticides.

poinsettia

For example, poinsettias are wonderful plants we all have around the house at holiday time. Why would we consider starting out with poinsettias? Well, they grow in a warm, moist greenhouse spending much of the time in the dark. This is the perfect breeding ground for molds and fungus. Workers in these greenhouses are exposed to a number of conventional pesticide treatments to deal with these problems.

The EPA likes products that improve safety, pose no threat to the environment and solve a problem that provides an economic benefit. It is not our first choice but, may end up being our best choice because of the reduction in environmental and toxicology testing we may have to submit.

Testing costs affect the bottom line (for good and for bad)

Why are we bananas about bananas?

One of the focus areas of our research involves a fungal pathogen of bananas….. a fruit we all love to eat. It seems bananas (Musca acuminata) are having a rather difficult time of it right now. The worst part is that it is deja vu all over again!

Bananas are under attack from Black Sigatoka Mycosphaerella fijiensis (Morelet) (see http://en.wikipedia.org/wiki/Black_Sigatoka ) which is decimating banana crops around the world.

Bananas are a bigger deal than you may think. They are the forth largest cash crop in the world after wheat, rice and corn. The average american consumes about 25 pounds of bananas each year and that amount is greater than apples and oranges combined. In Rwanda, per capita consumption is over 500 lbs. per year!

Here are a couple of references detailing the problem:

Black sigatoka: An increasing threat to banana cultivation  http://www.apsnet.org/edcenter/intropp/lessons/fungi/ascomycetes/Documents/0110-01F.pdf

Black sigatoka of Banana: A most important disease of a most important fruit

http://www.apsnet.org/publications/apsnetfeatures/Pages/BlackSigatoka.aspx

So, there is clearly a problem. In our greenhouse study, we were able to demonstrate equal control of Mycocosphaerella fijiensis compared to the conventional pesticide propiconazole. That’s a long way from a commercial product but, at least we are in the race to find a environmentally safe biological treatment before bananas disappear from your grocery shelves (its happened before!).