Provivi and the insect love story that never happens

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You known the basic pitch for dating sites from the relentless advertising of sites from eHarmony to FarmersOnly.com: that technology can make the world a better place by bringing couples together.

But what about the opposite?

Could a biotechnology succeed in reducing pests and the resultant damage to crops they bring — by making it nearly impossible for them to find mates and produce future pest generations?

Provivi’s Big Series B raise

What you might consider DisHarmony.com is a living reality at Provivi, which announced its first closing of $21 million of a $31.5 million Series B financing round led by Kairos Ventures, with participation from Spruce Capital and other existing investors. BASF Venture Capital and DuPont Pioneer also participated in the round as strategic investors.

Provivi is developing natural, affordable pheromone products for pest control and crop protection. Pheromones are substances that serve as highly selective attractants for insects allowing the control of deleterious pests while preserving beneficial insects.

These compounds elicit non-lethal, species-specific insect control through disrupting mating cycles, resulting in lower insect pest populations and significantly reducing crop damage and losses.

“We’re at an exciting stage in Provivi’s development,” said Dr. Pedro Coelho, Co-Founder and CEO of Provivi. “The Series B investment validates our continued progress to establishing pheromones as a universal foundation for integrated pest management.”

The Series B funds will support further development, testing, and commercialization of Provivi’s new pheromone products.

Whether its food or feedstock for the bioeconomy, crop protection is big business. In there are insecticides, fungicides, herbicides, and seed treatment.Earlier this year, DuPont was forced to shed a portion of its crop protection business, and realized $1.2 billion from the sale to FMC. And that’s just one portion, one company.

Overall, the sector raked in $62.87 billion in 2016 and is expected according to this report to grow to $87.83 billion by 2020.

Making Crop Protection more selective, or why Jane Goodall loves ProVivi

Hitherto, crop protection has not been all that selective. There have been a lot of hammers built to crush a fly. Sort of like the use of poison gas in the First World War, which could only be used in favorable wind conditions because, of course, the gas was just as deadly to friendlies as foes.

Changing the way that crop protection is done — that’s one of the reasons that, upon visiting the Provivi site, you’ll see a ringing endorsement from Jane Goodall.

The story behind the technology

CalTech’s Frances Arnold has picked up almost every major scientific prize short of the Nobel. Of all the discoveries coming out of her lab over the years, the demonstrations of the impact of something called ‘enzymatic cyclopropanation’ rank right at the top. It’s the foundational discovery set from which Provivi stems.

The report first came out in Science about five years ago, when Arnold’s team reported that they had learned how to modify an enzyme so that it catalyzed the formation of a cyclopropane ring.

The original application was anesthesia. But as the insecticide industry delved into the chrysanthemum — and crushed chrysanthemum powder has been used by the Chinese as a natural insecticide for more than 3,000 years — they discovered, at the heart of the matter, a set of esters and a cyclopropane core known as a pyrethrin, derived from the seed case of a Chrysanthemum varietal known as pyrethrum. Also known around the world as Persian powder.

These are the basis of most commercial household insecticides and also a base from which a lot of antibiotics are produced.

Making cyclopropane rings is, as the Aussies put it, hard yakka — that is, real tough work. And exclusively reserved for the world of synthetic chemistry rather than enzyme chemistry. The latter has more selectivity and precision. So, the word coming out of the Arnold Lab opened up a huge range of possibilities in making more selective insecticides.

Sustainable chemistry blogger David Rozzell (a former VP at Codexis) wrote in 2016:

I never expected an enzyme to do this. When I first learned about the discoveries from Frances Arnold’s lab at Caltech that demonstrated enzymatic cyclopropanation for the first time, I was amazed. I never imagined that an enzyme could catalyze a carbene transfer reaction, in water, with a diazo compound as the carbene source, to produce a chiral cyclopropane product.

Enzyme-catalyzed cyclopropanation was a surprising discovery, a true breakthrough reaction for an enzyme. I also assumed it would probably turn out to be an academic curiosity would be unlikely to find practical use.

But I continued to follow the development of this novel enzymatic cyclopropanation. During the ensuing months the reported turn-over numbers increased. Other carbene and nitrene transfer reactions were demonstrated. As the enzymes were improved through strategic mutations, yields increased dramatically and the production of single stereoisomers was demonstrated with high selectivity. 

What Provivi came up with

Flowing from the original discovery, they have engineered a pathway to create pheromones (a scent hormone that causes atraction) that completely mix up the insect romantic cycle. Faster than you can say “birth control”, it causes population collapse, but not in every species, just the target.

So you don’t get, for instance, unwanted bee population collapse while targeting a pest. The beneficial insects are unaffected. That’s the power of selectivity.

The 5 Competitive Edges

In all, Provivi focuses on five impacts as it tells its story. Here’s the Provivi pitch.

Natural. Harnessing the same pheromone molecules that insects use to communicate.

Effective. Patented technology that dramatically reduces pest populations and minimizes crop damage.

Safe. No harmful residues on crops and no side-effects to humans, beneficial insects (such as bees), or the environment.

Easy to Use. Fully compatible with existing delivery methods for large-field applications.

Affordable. Our pheromone-based practice is a cost-effective alternative to insecticides

The Bottom Line

Affordable. Effective. Safe, easy to use and natural. You probably couldn’t think up a more powerful combination of five terms for the advanced bioeconomy if you tried. Next steps are to proceed to deliver on that promise through scale-up, and more targets for more little critters.

At eHarmony, they say that Love is Closer then You Think. For these pesty insects, it looks like Provivi is making sure that it remains far, far away. Like a dating site run by Eeyore, Provivi is finding ways to make insects abandon the search for love. Seen at the insect level, it’s dystopian — but excellent news for growers and all of us who depend on nature’s bounty.

Reaction from the stakeholders

“This investment confirms the confidence that the industry has in Provivi’s technology,” said James Demetriades, Managing Partner of Kairos Ventures. “I am excited by Provivi’s continued progress in developing products which will improve the safety and sustainability of global food production.”

“We look forward to Provivi’s progress toward enabling pheromone applications for improved pest protection in row crops,” said Neal Gutterson, Vice President of Research & Development for DuPont Pioneer.