AT A GLANCE AGRICULTURE
BORAGEN Protecting plants with shapeshifting boron molecules
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thing in common: a structure based on boron. Today’s pesticides come from traditional carbon-, nitrogen-, sulfur-, or metal-based chemistry. Boron is overlooked, Liu says, because the activity of complex boron molecules can be hard to predict. Liu was introduced to the idea of bioactive boron molecules—and his future Boragen cofounders—at the start of his postdoctoral research at Pennsylvania State University. He met scientists who successfully deployed boron in treatments
very year, plant diseases and pests wipe out 20–40% of the world’s crops, according to the United Nations. And while trade has given farmers access to more markets, it has also helped spread serious diseases, like the strain of fusarium wilt fungus now threatening global banana production. Even though big agriculture firms introduce new pesticides every year, there is not an available solution for every pest problem. Indeed, two of today’s four top-selling fungicides were commercial-
Stronger spray Boragen is developing benzoxaborole fungicides that can be mixed with traditional fungicides. The two modes of action prevent disease organisms from developing resistance to the chemicals. Further, the boron-containing molecules’ effectiveness has been fine-tuned using one of two shapes to better fit the disease target.
or Trigonal benzoxaborole
Tetrahedral benzoxaborole
Benzoxaborole fungicide
C R E D I T: YA N G H . KU/C & EN / S H U TT E RSTOC K
Infected plants
+ Traditional fungicide
Each season
Treated plants
ized in the early 1960s; eventually organisms develop resistance to the old standbys. None are on hand to save bananas or the many crops vulnerable to pesticide-resistant diseases. “Agriculture needs a new chemical platform to help with issues like resistance,” says C. Tony Liu, cofounder and chief scientific officer of Boragen. Liu and his colleagues at Boragen have built a library of plantpest-killing chemicals that all have one
Fungal organism does not develop resistance
for skin infections and other diseases, proving that boron can be used to make safe, biologically active molecules. It turns out that agriculture has plenty of biological targets to pursue with the help of boron. That opportunity gave Boragen a spot at the new Research Triangle Park, N.C.-based AgTech Accelerator. Earlier this year, the company emerged from AgTech with $10 million in funding from accelerator investors including the Bill & Melinda Gates Foundation, Bayer, and Syngenta.
⚫ Launched: 2015 ⚫ Headquarters: Research Triangle Park, N.C. ⚫ Focus: Pest control for agriculture ⚫ Technology: Tunable boronbased molecules ⚫ Founders: Stephen J. Benkovic, Gerald Fink, C. Tony Liu, Paul Schimmel, and Lucy Shapiro ⚫ Funding or notable partners: $10 million from Bill & Melinda Gates Foundation, Arch Venture Partners, Flagship Pioneering, Bayer, and Syngenta Ventures Boragen’s compounds can control a range of fungal diseases in plants with a mode of action entirely different from that of traditional fungicides. What’s more, boron compounds have low toxicity to non-target species and work synergistically with traditional fungicides, the firm says. By using both modes of action, farmers can prevent the fungal organism from rallying its means of chemical resistance. Boragen’s lead compound is a benzoxaborole, which works by throwing a wrench in a cell’s protein-making machinery. It inhibits aminoacyl transfer RNA synthetases, enzymes responsible for attaching specific amino acids to tRNA. The resulting malformed protein doesn’t work the way it should, killing the pest. To fine-tune the activity of boron pesticides, scientists take advantage of boron’s unusual shape-shifting ability, Liu says. Boron compounds can easily be made into a trigonal planar shape or a three-dimensional tetrahedron to better fit a target site. The two shapes allow researchers to select a negative or neutral charge. Boragen now occupies greenhouse and laboratory space in Research Triangle Park, a hotbed of commercial agriculture research, and is testing its lead fungicide in field trials. Liu and his growing team of boron chemists and plant scientists are still exploring the many biological pathways that boron compounds can interrupt. In addition to beating fungal disease, boron chemistry could be used to combat nematodes and livestock parasites. “We are so excited and passionate about the boron atom,” Liu says. “It gives you flexibility that you can’t get with carbon.”—MELODY BOMGARDNER NOVEMBER 6, 2017 | CEN.ACS.ORG | C&EN
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