Ultra-high-throughput crystallographic screening platform for discovery of novel fusarium trichodiene synthase inhibitors

Overview

This solution offers an innovative approach to combating Fusarium infestation in crop species by targeting trichodiene synthase (TRI5), a key enzyme in fungal mycotoxin production. The platform leverages proprietary ultra-high-throughput X-ray crystallography screening combined with AI/ML-driven analytics to discover novel, potent, and less toxic TRI5 inhibitors. Unlike traditional screening methods that rely on pre-existing compound libraries, this approach generates direct structural evidence of target binding, enabling the creation of new, patentable chemistry with improved selectivity profiles.

The offering addresses a critical agricultural challenge: Fusarium fungi produce trichothecene mycotoxins that contaminate crops and pose serious health risks to humans and livestock. By inhibiting TRI5 at the molecular level, this technology aims to eliminate the deleterious effects of Fusarium infestation across multiple crop species.

Technical specifications

Key features:

• Proprietary ultra-high-throughput X-ray crystallography screening platform validated on numerous targets
• AI/ML analytics integrated with structural data for accelerated hit identification and lead optimization
• Diverse proprietary fragment library comprising 1,000 fragments
• Typical hit rates of 5-15%, with potential to reach up to 60%
• Rapid screening capability: entire 1,000-fragment library can be screened within one week
• Direct evidence of TRI5 binding through high-resolution crystal structures
• Capability to engineer compounds around resistance mutations
• Generation of novel, patentable chemical entities
• Integration of biochemical assays and cell-based assays for potency optimization
• Complementary Fusarium-specific expertise to inform biological and biochemical studies

Technology readiness level

The crystallography platform has been validated across numerous targets through prior successful campaigns. The current initiative is at the target setup and screening stage for Fusarium TRI5. The proposed workflow begins with generating multiple high-resolution TRI5 crystal structures, followed by fragment library screening, hit expansion guided by crystal structures, and progression through biochemical and cell-based assays to deliver an optimized lead compound. This approach is positioned to accelerate the path from initial screening to development candidate compared to conventional methods.