AI Insight
Researchers have successfully reprogrammed a bacterial sensor protein (MphR) to detect four valuable plant-based compounds called sesquiterpenes: valencene, nootkatone, artemisinin, and cedrol. By introducing six specific mutations to the sensor protein, they reduced the size of its binding pocket, enabling it to recognize these smaller molecules. The modified biosensor showed 15-20-fold improved sensitivity when paired with an optimized fluorescence reporter, creating a versatile tool for detecting multiple sesquiterpenes.
Why it matters
This biosensor addresses a major bottleneck in producing valuable plant compounds that are currently difficult and expensive to obtain. It enables high-throughput screening of engineered bacteria or yeast to identify the best producers of these compounds, which are used in flavors, fragrances, and pharmaceuticals including the antimalarial drug artemisinin.
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⚠️ Preprint – Noch nicht peer-reviewed
Dieser Artikel wurde noch nicht von unabhängigen Experten begutachtet. Die Ergebnisse sind vorläufig und sollten mit Vorsicht interpretiert werden.
Terpenes are a large, diverse class of natural products used as flavors, fragrances, pharmaceuticals, and more, yet obtaining them often requires either large quantities of biomass or complex chemical reactions. Directed evolution of key enzymes and pathways could improve biosynthetic yields, but most sesquiterpenes lack high-throughput screening methods to search large libraries of variants. To alleviate this bottleneck, we developed the first reported genetically encoded biosensor to detect four highly valuable sesquiterpenes: valencene, nootkatone, artemisinin, and cedrol. Starting with the macrolide transcription factor biosensor MphR, we screened a panel of mutants against the four sesquiterpenes, including MphR-13 (T17N/V18I/K21L/S106L/H147L/P161L), which readily detected all four sesquiterpenes. Computational modeling showed that the mutations reduced the size of the ligand-binding pocket compared with the wild type, which positively correlated with the biosensor’s fluorescence output. Additionally, swapping the fluorescence reporter improved the sensor’s response 15-20-fold, yielding a generalist sesquiterpene biosensor that can be further developed and applied to the directed evolution of sesquiterpene biosynthesis.