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[学术文献 ] Computational design of serine hydrolases 进入全文
science
The design of enzymes with complex active sites that mediate multistep reactions remains an outstanding challenge. With serine hydrolases as a model system, we combined the generative capabilities of RFdiffusion with an ensemble generation method for assessing active site preorganization to design enzymes starting from minimal active site descriptions. Experimental characterization revealed catalytic efficiencies (kcat/Km) up to 2.2x105 M−1 s−1 and crystal structures that closely match the design models (Cα RMSDs < 1 Å). Selection for structural compatibility across the reaction coordinate enabled identification of new catalysts in low-throughput screens with five different folds distinct from those of natural serine hydrolases. Our de novo approach provides insight into the geometric basis of catalysis and a roadmap for designing enzymes that catalyze multistep transformations.
[前沿资讯 ] Startup grows egg proteins in potato fields 进入全文
nature biotechnology
Molecular farmers Maya Sapir-Mir (left) and Raya Liberman-Aloni are taking a global culinary favorite and transforming it into a low-cost bioreactor to manufacture egg protein. They set up PoLoPo in 2022 to engineer potato plants to produce egg-white protein without the need for expensive bioreactors. The company, which is based in Ness Ziona, Israel, has begun its first field trial growing the protein-rich tuber.PoLoPo has also developed potatoes with enhanced production of the protein patatin, which is found naturally in the tuber. The PoLoPo team genetically tweaked the potato genome to express genes that shift the plant’s metabolism towards protein production and accumulation in tubers. The team is now seeking approval from the US Department of Agriculture for the patatin-rich potatoes. PoLoPo received backing from the German venture capital firm FoodLabs. Other genetically modified potatoes are already available for sale in the USA. J.R. Simplot, based in Boise, Idaho, is already selling genetically modified Russet Burbank, Ranger Russet and Atlantic potatoes, which were created to resist bruising and potato blight.
[政策法规 ] Engineering Tomorrow: DARPA’s Push into the Frontier of Synthetic Biology 进入全文
美国国防高级研究计划局 (DARPA)
DARPA aims to tackle precisely these scaling nightmares by infusing them with fresh tools. Picture an AI-powered design-build-test cycle that runs round the clock, generating tens of thousands of experimental variants in days. Such an approach demands custom-built platforms for lab automation, capable of operating at volumes and speeds beyond what any typical bench scientist can do. Koeris insists that the future of SynBio depends on different defaults for experimental volumes, frequencies, and data capture. Instead of shaping everything around a human with a pipette, we can build microfluidic or robotic systems that revolve around the optimum scale for the experiment. He wants to eliminate the “little weeds” that often trap researchers when they try to interpret gene expression networks or cellular behaviors one micro-liter at a time. A neural network, on the other hand, doesn’t bat an eyelid at millions of data points.
[科研项目 ] Enveda’s fusion of natural product insights and AI just got a boost with a new CFO at the helm and $130M in fresh capital 进入全文
Enveda公司
Strengthening Enveda’s momentum is the recently announced $130 million Series C funding round, led by Kinnevik and FPV, with participation from new and existing investors, including Baillie Gifford, Premji Invest, Lingotto Innovation, Lux Capital, Dimension Capital, True Ventures, Cresset Partners, The Nature Conservancy, and Henry R. Kravis. This round brings Enveda’s total funding to $360 million, fortifying its ability to advance its pipeline of 10 Development Candidates, additional discovery programs, and a state-of-the-art AI platform.
[前沿资讯 ] Data hazards in synthetic biology 进入全文
Synthetic Biology
Data science is playing an increasingly important role in the design and analysis of engineered biology. This has been fueled by the development of high-throughput methods like massively parallel reporter assays, data-rich microscopy techniques, computational protein structure prediction and design, and the development of whole-cell models able to generate huge volumes of data. Although the ability to apply data-centric analyses in these contexts is appealing and increasingly simple to do, it comes with potential risks. For example, how might biases in the underlying data affect the validity of a result and what might the environmental impact of large-scale data analyses be? Here, we present a community-developed framework for assessing data hazards to help address these concerns and demonstrate its application to two synthetic biology case studies. We show the diversity of considerations that arise in common types of bioengineering projects and provide some guidelines and mitigating steps. Understanding potential issues and dangers when working with data and proactively addressing them will be essential for ensuring the appropriate use of emerging data-intensive AI methods and help increase the trustworthiness of their applications in synthetic biology.
[学术文献 ] Diploid inbred-based hybrids: fast-forward breeding approach in potatoes 进入全文
PHYSIOLOGY AND MOLECULAR BIOLOGY OF PLANTS
Following the identification of the self-compatibility gene (Sli) in diploid potatoes two decades ago, the breeding of inbred based diploid hybrid potatoes made its way. Tetraploid potatoes have a long history of cultivation through domestication and selection. Tetrasomic inheritance, heterozygosity and clonal propagation complicate genetic studies, resulting in a low genetic gain in potato breeding. Diploid hybrid TPS potato breeding, similar to the developments in hybrid maize, was pursued as an alternative to the genetic improvement of potatoes. However, several challenges, like self-incompatibility and high inbreeding depression associated with diploid potatoes, must be overcome to develop inbred lines in potatoes. Moreover, the inbred lines must retain good fertility and vigour for hybrid breeding. Good progress has been made by creating di-haploids of popular varieties, mapping self-incompatibility inhibitor gene, understanding the genetic basis of inbreeding depression, and identifying genomic regions for deleterious alleles and fertility. Further, the genome sequencing of diploid inbred lines has revealed the genetics of key traits associated with potato breeding. This article discussed these insights and summarized the progress of diploid hybrid TPS potato breeding. Recent advances in genetic and genomic research and genome editing technology have shown promise for this technology's success and far-reaching implications.