Fecha de publicación:
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Fuente:
PubMed "plant biotechnology"
Mol Cell. 2026 Sep 24:S1097-2765(26)00617-9. doi: 10.1016/j.molcel.2026.08.028. Online ahead of print.ABSTRACTDespite the significant progress made in recent years, current AI-driven protein engineering methods often suffer from iterative experimental validation, limited success rates, modest improvements, and/or high computational costs. Moreover, their utility for evolving plant proteins remains unexplored. Here we present unZipro, an efficient, scalable, and generalizable framework for zero-shot, in silico protein evolution. unZipro integrates a compact, pre-trained inverse folding model with meta-learning to derive family-specific fitness landscapes. We demonstrate unZipro's ability to directly identify high-activity variants from minimal libraries (∼10 candidates) with an average success rate of 61% across nine diverse proteins, achieving up to a 28-fold increase in the gene-editing activity of T5E-CasΦ2 fusion variants. Leveraging unZipro, we developed state-of-the-art plant gene-editing nucleases, superior firefly luciferase variants, enhanced rice transcription factors, and barley-derived antiviral proteins with elevated potency. Overall, unZipro represents a new paradigm for cost-effective, widely accessible, and transformative protein engineering in biology, biotechnology, and agriculture.PMID:42785296 | DOI:10.1016/j.molcel.2026.08.028