Babonis Leslie S, Hahn Daniel A, Liu Allen P, Widhalm Joshua R
Department of Ecology and Evolutionary Biology, Cornell University, Ithaca, NY 14853, USA.
Department of Entomology and Nematology, University of Florida, Gainesville, FL 32611, USA.
Integr Comp Biol. 2025 Sep 13;65(2):198-215. doi: 10.1093/icb/icaf107.
Nature has already solved many challenges that synthetic biology seeks to address. At the same time, high-throughput platforms and artificial intelligence-driven design tools are redefining the landscape of synthetic biology. By integrating evolutionary insights with new enabling technologies, we are poised to move beyond modifying existing traits to engineering entirely new cellular functions. This series of vignettes explores how phenotypic engineering, inspired by nature's most extreme adaptations, represents the next frontier in synthetic biology. We first make a case for the importance of continuing to explore nature by examining how foundational discoveries in molecular biology, motivated by curiosity to understand how life works rather than immediate application, laid the groundwork for modern applications in biology. Next, we discuss how evolution produced novel cell types with extraordinary properties and how leveraging these innovations can enable the creation of radical phenotypes beyond natural evolutionary constraints. Then, we explore the potential of artificial cells, constructed from the bottom up, as experimental platforms for studying genotype-phenotype relationships and testing evolutionary principles in real time. Finally, we argue that engineering radical phenotypes and emergent traits will require better investment in basic science, infrastructure, and graduate training to avoid bottlenecking innovation. History has shown that committing to basic science results in transformative solutions with far-reaching societal and economic benefits. By drawing inspiration from evolution and expanding synthetic biology beyond traditional model systems, we can push current boundaries to open new avenues for fundamental discovery and technological advances to stimulate the bioeconomy.
大自然已经解决了合成生物学试图应对的许多挑战。与此同时，高通量平台和人工智能驱动的设计工具正在重新定义合成生物学的格局。通过将进化见解与新的使能技术相结合，我们有望从修改现有性状迈向设计全新的细胞功能。本系列短文探讨了受自然界最极端适应启发的表型工程如何代表合成生物学的下一个前沿领域。我们首先通过研究分子生物学中的基础发现来论证继续探索自然的重要性，这些发现源于理解生命如何运作的好奇心而非直接应用，为生物学的现代应用奠定了基础。接下来，我们讨论进化如何产生具有非凡特性的新型细胞类型，以及利用这些创新如何能够创造超越自然进化限制的激进表型。然后，我们探索自下而上构建的人工细胞作为研究基因型 - 表型关系和实时测试进化原理的实验平台的潜力。最后，我们认为设计激进表型和涌现性状将需要在基础科学、基础设施和研究生培训方面进行更好的投资，以避免创新瓶颈。历史表明，致力于基础科学会带来具有深远社会和经济效益的变革性解决方案。通过从进化中汲取灵感并将合成生物学扩展到传统模型系统之外，我们可以突破当前界限，为基础发现和技术进步开辟新途径，以刺激生物经济。
