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[学术文献 ] Synthetic Biology in Natural Product Biosynthesis 进入全文

Chemical Reviews

Synthetic biology has played an important role in the renaissance of natural products research during the post-genomics era. The development and integration of new tools have transformed the workflow of natural product discovery and engineering, generating multidisciplinary interest in the field. In this review, we summarize recent developments in natural product biosynthesis from three different aspects. First, advances in bioinformatics, experimental, and analytical tools to identify natural products associated with predicted biosynthetic gene clusters (BGCs) will be covered. This will be followed by an extensive review on the heterologous expression of natural products in bacterial, fungal and plant organisms. The native host-independent paradigm to natural product identification, pathway characterization, and enzyme discovery is where synthetic biology has played the most prominent role. Lastly, strategies to engineer biosynthetic pathways for structural diversification and complexity generation will be discussed, including recent advances in assembly-line megasynthase engineering, precursor-directed structural modification, and combinatorial biosynthesis.

[前沿资讯 ] 中科院天津工业生物技术研究所在大语言模型助力生物制造应用方面取得进展 进入全文

中科院天津工业生物技术研究所

近日,中国科学院天津工业生物技术研究所生物设计中心开发了基于LLMs的SynBioGPT菌种改造专家系统(https://synbiogpt.biodesign.ac.cn)。该系统已通过海外科学家验证,取得了良好的效果。相关研究进一步全面分析了AI大语言模型在合成生物学应用方面的最新进展,深入探讨了利用这些AI大模型推动细胞工厂设计和代谢工程菌种改造的可行路径。SynBioGPT整合了51,777篇文献摘要和23,318篇开放获取全文PDF,测试了LLMs在合成生物学问题上的表现。结合检索增强生成(Retrieval-Augmented Generation,RAG)技术后,LLMs的回答准确性从25%显著提升至85%,其中Qwen1.5和Llama3模型表现尤为突出。为了进一步验证LLMs在生物制造中的应用潜力,团队进一步分析了其在生物序列建模、细胞工厂开发和自驱动实验室(Self-Driving Laboratories,SDL)中可能发挥的作用。首先,LLMs在处理DNA、RNA和蛋白质序列数据中具有独特优势,特别是在蛋白质语言模型中能够生成通用表示,为构建AI虚拟细胞(AI Virtual Cell,AIVC)奠定基础。其次,在细胞工厂开发中,LLMs通过整合文献数据和实验报告,加速了酶工程、途径设计和发酵优化的设计–构建–测试–学习(DBTL)周期,其能够提取关键特征并与代谢模型结合,从而提高机器学习预测能力并优化生物制造效率。最后,作为智能代理,LLMs通过任务规划、实验设计和数据分析推动生物制造向SDL范式转变,SDL结合机器人技术与人类监督,能够实现从任务分解到实验执行的全流程自动化,为未来智能化生产奠定基础。综上所述,该研究详细阐明了LLMs在合成生物学知识合成和生物制造智能化中的应用机制,展示了其在提升生产效率和可持续性方面的潜力。同时,该研究也为LLMs在合成生物学中的应用提供了新的视角,拓展了其在生物催化、药物开发和环保技术中的研究领域。

[前沿资讯 ] Green recipe: Engineered yeast boosts D-lactic acid production 进入全文

EurekAlert

Seeking a more efficient way to produce D-lactic acid, the team turned to Komagataella phaffii, a yeast capable of utilizing methanol. Their goal was to pinpoint the optimal combination of D-lactate dehydrogenase (D-LDH) genes and promoters in K. phaffii that would maximize the yeast’s ability to produce D-lactic acid from methanol. D-LDH is a key enzyme responsible for converting precursor molecules into D-lactic acid, while promoters are DNA sequences that regulate gene expression. After testing five different D-LDH genes and eight promoters, the researchers identified an ideal mix that boosted D-lactic acid production by 1.5 times compared to other methanol-based methods. “To the best of our knowledge, our engineered yeast achieved the highest-ever reported yield using methanol as the sole carbon source,” Yamada said. These findings show that engineered yeast strains can be tailored to produce a wide range of useful compounds for commercial use. With growing global concerns over fossil fuel depletion and environmental impact, the ability to synthesize chemicals from renewable carbon sources like methanol is deemed a critical advancement for sustainability. “This study demonstrates that by carefully optimizing gene and promoter combinations, we can significantly enhance the efficiency of microbial processes, offering a viable alternative to traditional, petroleum-based chemical production,” Yamada said. The study was published in Biotechnology for Biofuels and Bioproducts.

[学术文献 ] Generative artificial intelligence for enzyme design: Recent advances in models and applications 进入全文

CURRENT OPINION IN GREEN AND SUSTAINABLE CHEMISTRY

Enzyme catalysis is a key enabling technology for green and sustainable production of chemicals. Developing suitable enzymes is at the heart of this technology, which is currently changing by Artificial Intelligence (AI) such as machine learning. AI-based methods were used for enzyme discovery and design. We review the recent advances in generative AI models for enzyme design, with a particular focus on those that have been validated by experiments. Furthermore, we discuss the applications of the enzymes designed by generative AI, including artificial luciferases, non-heme iron (II)-dependent oxygenases, and P450 enzymes. We provide our opinions on several current issues encountered in computational enzyme design. With the fast development of new generative models in enzymes and the implementation of these models by the research community, we believe that the precise design of efficient enzymes with new catalytic functions and/or potential industrial applications will be a mature method in the near future.

[前沿资讯 ] Illinois researchers develop next-generation organic nanozymes and point-of-use system for food and agricultural uses 进入全文

EurekAlert

Nanozymes are synthetic materials that have enzyme-like catalytic properties, and they are broadly used for biomedical purposes, such as disease diagnostics. However, inorganic nanozymes are generally toxic, expensive, and complicated to produce, making them unsuitable for the agricultural and food industries. A University of Illinois Urbana-Champaign research team has developed organic-material-based nanozymes that are non-toxic, environmentally friendly, and cost effective. In two new studies, they introduce next-generation organic nanozymes and explore a point-of-use platform for molecule detection in agricultural products.“The first generation of organic-compound-based (OC) nanozymes had some minor drawbacks, so our research group worked to make improvements. The previous OC nanozymes required the use of particle stabilizing polymers having repeatable functional groups, which assured stability of the nanozyme’s nanoscale framework, but didn’t achieve a sufficiently small particle size,” said lead author Dong Hoon Lee, who completed his Ph.D. from the Department of Agricultural and Biological Engineering (ABE), part of the College of Agricultural, Consumer and Environmental Sciences and The Grainger College of Engineering at the U. of I. In the new iteration, they used a core amino acid (L- alanine) and polyethylene glycol as constituent materials and a novel particle synthesis technique that allowed them to bring the particle size down to less than 100 nanometers. This nanozyme resembles the physical framework and mimics the catalytic activity of target enzymes. 

[科技报告 ] OECD Synthetic biology in focus: Policy issues and opportunities in engineering life 进入全文

OECD

Synthetic biology promises to revolutionise a swath of industrial activities and create new ones by tailoring living systems to produce a range of products to boost economies, transform health and contribute to solving grand societal challenges. In 2023 and 2024, over sixty experts from around the globe came together regularly to explore where synthetic biology will have the most impact, identify the challenges and opportunities in developing and deploying synthetic biology around the world, and to explore areas where policy could help. This working paper provides a synthesis of this scoping activity, providing an accessible text for those new to the rapidly evolving area of synthetic biology.

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