生物设计研究(英文)最新文献_第2页

Metabolic engineering of Escherichia coli for de novo production of lauryl glucoside. 大肠杆菌重新生产月桂基葡萄糖苷的代谢工程。

IF 4.7

生物设计研究(英文) Pub Date : 2025-09-04 eCollection Date: 2025-12-01 DOI: 10.1016/j.bidere.2025.100045

Kasimaporn Promubon, Chaiwat Arjin, Chayakorn Pumas, Aussara Panya, Patrik R Jones, Pachara Sattayawat

{"title":"Metabolic engineering of Escherichia coli for de novo production of lauryl glucoside.","authors":"Kasimaporn Promubon, Chaiwat Arjin, Chayakorn Pumas, Aussara Panya, Patrik R Jones, Pachara Sattayawat","doi":"10.1016/j.bidere.2025.100045","DOIUrl":"https://doi.org/10.1016/j.bidere.2025.100045","url":null,"abstract":"Lauryl glucoside, a non-ionic surfactant used in various cosmetic products, is valued for its biodegradability and gentleness on the skin. However, its current production through chemical synthesis is considered unsustainable, necessitating the search for alternative methods. In this work, we engineered Escherichia coli BL21(DE3) with a novel lauryl glucoside biosynthetic pathway. Optimisation of 1-dodecanol, a lauryl glucoside precursor, was first implemented. Under optimised conditions, the strain produced 1-dodecanol at a titre of 185.39 ± 3.62 mg/L and a yield of 11.60 ± 0.29 mg/g glucose. These conditions were subsequently used to identify UDP-glycosyltransferases capable of converting 1-dodecanol to lauryl glucoside. Among six UDP-glycosyltransferases, MtH2 from Medicago truncatula showed the highest activity, with a titre and a yield of 0.72 ± 0.07 mg/L and 0.06 ± 0.004 mg/g glucose, respectively. The lauryl glucoside biosynthesis by MtH2 was confirmed using HPLC and targeted LC-MS. Moreover, the limited availability of 1-dodecanol was primarily identified as the bottleneck in this pathway. Supplementing the cells with twice the amount of 1-dodecanol led to an increase in lauryl glucoside production, achieving a titre of 13.44 ± 0.21 mg/L and a yield of 1.35 ± 0.04 mg/g glucose. Fermentation products of all strains were also monitored and suggested the redirection of carbon flux from acetate to the desired products. These findings demonstrate the successful characterisation of a newly designed lauryl glucoside biosynthetic pathway in engineered E. coli and highlight substrate limitation as a bottleneck in the pathway offering a sustainable alternative to traditional production methods.","PeriodicalId":56832,"journal":{"name":"生物设计研究(英文)","volume":"7 4","pages":"100045"},"PeriodicalIF":4.7,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13109341/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147790161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

From machine learning to multimodal models: The AI revolution in enzyme engineering. 从机器学习到多模态模型：酶工程中的人工智能革命。

IF 4.7

生物设计研究(英文) Pub Date : 2025-08-29 eCollection Date: 2026-03-01 DOI: 10.1016/j.bidere.2025.100044

Ziyan Shi, Shuping Xu, Sihan Xue, Kaiming Chen, Yifan Lu, Feiyue Wang, Siyu Long, Yannan Tian, Peng Zhang, Jianing Wang, Yanhui Gu, Junsheng Zhou, Hao Zhou, Shuaiqi Meng, Haiyang Cui

{"title":"From machine learning to multimodal models: The AI revolution in enzyme engineering.","authors":"Ziyan Shi, Shuping Xu, Sihan Xue, Kaiming Chen, Yifan Lu, Feiyue Wang, Siyu Long, Yannan Tian, Peng Zhang, Jianing Wang, Yanhui Gu, Junsheng Zhou, Hao Zhou, Shuaiqi Meng, Haiyang Cui","doi":"10.1016/j.bidere.2025.100044","DOIUrl":"https://doi.org/10.1016/j.bidere.2025.100044","url":null,"abstract":"Protein engineering is a powerful tool for applications spanning synthetic biology, biocatalysis, and drug discovery. Recent advances in artificial intelligence (AI), from conventional machine learning (ML) algorithms to large-scale pre-trained protein models, have greatly accelerated enzyme engineering field entering a data-driven era. This review provides a guidance map of current enzyme engineering tasks and builds an integrative perspective on AI methods, model types, landmark tasks, and data resources. We begin by delineating the core modeling tasks in enzyme engineering, which include encompassing function annotation, structural modeling, and property prediction and by reviewing recent advances alongside dominant algorithmic frameworks. Next, we outlined the evolution of AI into enzyme engineering, tracing its progression through four stages: classical machine learning approaches, deep neural networks, protein language models (pLMs), and emerging multimodal architectures. Finally, we highlight four trends that are redefining the landscape of AI-driven enzyme design: (i) the replacement of handcrafted features with unified, token-level embeddings; (ii) a shift from single-modal models toward multimodal, multitask systems; (iii) the emergence of intelligent agents capable of reasoning; and (iv) a movement beyond static structure prediction toward dynamic simulation of enzyme function. Together, these developments are paving the way for intelligent, generalizable, and mechanistically interpretable AI platforms poised to synthetic biology.","PeriodicalId":56832,"journal":{"name":"生物设计研究(英文)","volume":"8 1","pages":"100044"},"PeriodicalIF":4.7,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13109336/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147790292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A comprehensive review on violacein production by microbial fermentation. 微生物发酵生产紫罗兰素综述。

IF 4.7

生物设计研究(英文) Pub Date : 2025-08-21 eCollection Date: 2025-09-01 DOI: 10.1016/j.bidere.2025.100043

Qining Zhang, Jiahui Yang, Lu Mou, Yujia Jiang, Jorge Barriuso, Feng Guo, Fengxue Xin, Min Jiang

{"title":"A comprehensive review on violacein production by microbial fermentation.","authors":"Qining Zhang, Jiahui Yang, Lu Mou, Yujia Jiang, Jorge Barriuso, Feng Guo, Fengxue Xin, Min Jiang","doi":"10.1016/j.bidere.2025.100043","DOIUrl":"10.1016/j.bidere.2025.100043","url":null,"abstract":"Violacein is a natural purple secondary metabolite with a wide range of biological activities including antibacterial, anticancer, antioxidant, and antiparasitic properties, rendering it a highly promising candidate for applications in medicine, agriculture, and food industries. Despite its availability from natural sources, a profound understanding of its production mechanisms has long been lacking. High-level production of violacein has been achieved through integrated strategies, including heterologous expression of its biosynthetic pathway in recombinant strains, enhancement of tryptophan precursor supply, and optimization of fermentation conditions. These approaches offer a flexible and scalable platform for violacein biosynthesis. Furthermore, recent efforts have focused on utilizing agro-industrial waste as a cost-effective and sustainable feedstock to further improve production efficiency and environmental compatibility. This review provides a comprehensive overview of the latest advancements in violacein production, examines the challenges associated with its application, and proposes strategies for optimizing gene expression, refining fermentation protocols, and utilizing low-cost raw materials to facilitate the efficient and sustainable violacein production.","PeriodicalId":56832,"journal":{"name":"生物设计研究(英文)","volume":"7 3","pages":"100043"},"PeriodicalIF":4.7,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12710047/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145783708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

DeepCodon: A deep learning codon-optimization model to enhance protein expression. DeepCodon：一个深度学习密码子优化模型，以提高蛋白质表达。

IF 4.7

生物设计研究(英文) Pub Date : 2025-08-12 eCollection Date: 2025-12-01 DOI: 10.1016/j.bidere.2025.100042

Xudong Han, Xiaotong Shao, Shuo Liu, Zhenkun Shi, Rong Huang, Huanyu Chu, Hejian Zhang, Ruoyu Wang, Haoran Li, Xiaoping Liao, Jian Cheng, Huifeng Jiang

{"title":"DeepCodon: A deep learning codon-optimization model to enhance protein expression.","authors":"Xudong Han, Xiaotong Shao, Shuo Liu, Zhenkun Shi, Rong Huang, Huanyu Chu, Hejian Zhang, Ruoyu Wang, Haoran Li, Xiaoping Liao, Jian Cheng, Huifeng Jiang","doi":"10.1016/j.bidere.2025.100042","DOIUrl":"https://doi.org/10.1016/j.bidere.2025.100042","url":null,"abstract":"Codon optimization enhances heterologous gene expression by modulating synonymous codon usage, a critical task in genetic engineering and synthetic biology. Achieving optimal expression requires balancing multiple interdependent factors, such as host codon bias, GC content and mRNA secondary structure, turning optimization into a challenging multiobjective problem. Here, we introduce DeepCodon, a novel deep learning tool focused on preserving functionally important rare codon clusters, which are often overlooked in previous methods. Using Escherichia coli as the host species for gene expression, a protein-CDS translation model was first trained on 1.5 million natural Enterobacteriaceae sequences and then fine-tuned with highly expressed genes. To protect functionally important rare codon clusters, we integrated a conditional probability strategy that preserves conserved rare codons. Compared with conventional approaches, DeepCodon generates sequences that better match host preferences, achieves superior in silico metrics and maintains critical rare codons. Experimental validation of seven low-yield P450s and thirteen AI-designed G3PDHs in E. coli revealed that DeepCodon outperformed traditional methods in nine cases. These results demonstrate DeepCodon's potential as a practical solution for codon optimization.","PeriodicalId":56832,"journal":{"name":"生物设计研究(英文)","volume":"7 4","pages":"100042"},"PeriodicalIF":4.7,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13109293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147790222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Computational tools for nonnatural pathway design: Algorithms, applications, and challenges. 非自然路径设计的计算工具：算法、应用和挑战。

IF 4.7

生物设计研究(英文) Pub Date : 2025-07-26 eCollection Date: 2025-09-01 DOI: 10.1016/j.bidere.2025.100041

Yushuo Liu, Fan Wei, Xiaoping Liao, Xiaogui Deng, Qianqian Yuan, Hongwu Ma

{"title":"Computational tools for nonnatural pathway design: Algorithms, applications, and challenges.","authors":"Yushuo Liu, Fan Wei, Xiaoping Liao, Xiaogui Deng, Qianqian Yuan, Hongwu Ma","doi":"10.1016/j.bidere.2025.100041","DOIUrl":"10.1016/j.bidere.2025.100041","url":null,"abstract":"With the rapid advancements in sustainable development and green chemistry, biotransformation has become increasingly pivotal in the synthesis of bulk chemicals and high-value products. Because natural evolution predominantly favors cellular survival, many valuable compounds, such as 2,4-dihydroxybutanoic acid and 1,2-butanediol, lack corresponding biosynthetic pathways in nature. This limitation calls for the development of fully nonnatural metabolic pathways. By enabling modular design and incorporating novel reactions, such pathways allow efficient de novo synthesis of compounds without known natural biosynthetic pathways. Nonetheless, their implementation may introduce new challenges, such as increased metabolic burden and the accumulation of toxic intermediates. Expanding the scope and efficiency of biotransformation through rational nonnatural pathways has become a key challenge. To address this, researchers have developed various computational methods for nonnatural pathway design, and two major types of methods, template-based and template-free methods, are reviewed here. We evaluate their practical applications in guiding the construction of microbial cell factories and analyze their effectiveness. Additionally, we compiled 55 experimentally validated nonnatural pathways from recent literature to establish a dataset for evaluating the strengths and limitations of these pathway design methods. By simulating a wide range of experimentally verified pathways, we highlight the gaps between computational predictions and empirical feasibility. Finally, we propose potential strategies to bridge these gaps, offering theoretical insights and practical guidance for integrating computational tools with experimental synthetic biology.","PeriodicalId":56832,"journal":{"name":"生物设计研究(英文)","volume":"7 3","pages":"100041"},"PeriodicalIF":4.7,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12709947/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145783778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Engineered RNA-based activation system for coronavirus sensing in live cells. 在活细胞中检测冠状病毒的工程化rna激活系统。

IF 4.7

生物设计研究(英文) Pub Date : 2025-07-17 eCollection Date: 2025-09-01 DOI: 10.1016/j.bidere.2025.100040

Leiping Zeng, Christian Otero, Lei S Qi

{"title":"Engineered RNA-based activation system for coronavirus sensing in live cells.","authors":"Leiping Zeng, Christian Otero, Lei S Qi","doi":"10.1016/j.bidere.2025.100040","DOIUrl":"10.1016/j.bidere.2025.100040","url":null,"abstract":"Real-time sensing of viral infection in live cells is crucial for virology research and antiviral development. However, existing methods face challenges of low signal sensitivity and the necessity for viral manipulation and cell fixation. Here, we develop a Viral-Engineered RNA-based Activation System (VERAS) that harnesses the viral replicase to induce transgene expression upon viral infection. VERAS is designed to detect real-time viral transcription and replication in live cells, which can trigger the translation of reporter and therapeutic genes. By integrating a viral packaging sequence, VERAS can also be transmitted to neighboring cells through progeny virions, effectively acting as a 'Trojan Horse'. The negative-stranded VERAS elements demonstrated effective detection of several coronaviruses, including 229E and OC43, due to the conservation of cis-acting RNA structures across coronaviruses. Notably, VERAS functions as a dual-purpose system, acting both as an infection detector and inducible antiviral system. VERAS has the potential for basic virology research applications and can be adopted in improving the inducible expression of mRNA medicines for future coronaviruses.","PeriodicalId":56832,"journal":{"name":"生物设计研究(英文)","volume":"7 3","pages":"100040"},"PeriodicalIF":4.7,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12710057/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145783743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Recent advances of engineered probiotics for therapeutic applications. 工程益生菌治疗应用的最新进展。

IF 4.7

生物设计研究(英文) Pub Date : 2025-07-15 eCollection Date: 2025-09-01 DOI: 10.1016/j.bidere.2025.100039

Lu Zhang, Na Chen, Haofeng Chen, Chaoqun Tang, Junyi Wang, Yan Wang, Yang Zhang, Hao Guo, Jifeng Yuan

引用次数: 0

Biosynthesis of poly(3-hydroxybutyrate-co-lactate) using an NADH regeneration strategy in E. coli. 利用NADH再生策略在大肠杆菌中合成聚（3-羟基丁酸-乳酸）。

IF 4.7

生物设计研究(英文) Pub Date : 2025-06-06 eCollection Date: 2025-09-01 DOI: 10.1016/j.bidere.2025.100027

Ju Wu, Xuan Gong, Pengye Guo, Yanzhe Shang, Yuanchan Luo, Hui Wu

{"title":"Biosynthesis of poly(3-hydroxybutyrate-co-lactate) using an NADH regeneration strategy in E. coli.","authors":"Ju Wu, Xuan Gong, Pengye Guo, Yanzhe Shang, Yuanchan Luo, Hui Wu","doi":"10.1016/j.bidere.2025.100027","DOIUrl":"10.1016/j.bidere.2025.100027","url":null,"abstract":"In this study, a platform was constructed for the efficient biosynthesis of a lactate-based copolymer using a phosphite dehydrogenase (PtxD)-based NADH regeneration strategy. PtxD catalyzes the conversion of phosphite to phosphate while reducing NAD + to NADH. The latter is an essential cofactor for lactate synthesis in Escherichia coli. This strategy allows the decoupling of NADH regeneration from carbon metabolism flow, providing sufficient NADH for lactate synthesis. Different concentrations of isopropyl β-d-1-thiogalactopyranoside (IPTG) were used to control the intensity of PtxD expression, and the lactate fraction in the copolymer synthesized by the engineered strain ranged from 6.2 to 16.7 mol%. The ptxD gene was integrated into the genome of strain WJPCTP-01, which successfully synthesized 3.24 g/L P(3HB-co-23.0 mol% LA) and 2.23 g/L P(3HB-co-39.0 mol% LA) using glucose and xylose as substrates, respectively, in shake flask cultures. In 5 L bioreactor fermentations, the titer of P(3HB-co-41.3 mol% LA) reached 8.57 g/L, with a synthesis rate of 0.12 g/L/h when xylose was used as a substrate. These findings indicate that the PtxD-based NADH regeneration strategy enhances lactate synthesis without any significant negative impact on bacterial growth or the synthesis of P(3HB-co-LA).","PeriodicalId":56832,"journal":{"name":"生物设计研究(英文)","volume":"7 3","pages":"100027"},"PeriodicalIF":4.7,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12709964/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145783749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A framework for challenges and solutions in biodesign research. 生物设计研究中的挑战和解决方案的框架。

IF 4.7

生物设计研究(英文) Pub Date : 2025-06-04 eCollection Date: 2025-09-01 DOI: 10.1016/j.bidere.2025.100029

Xiaohan Yang, Zhihua Jiang, Shihui Yang, Zong-Ming Cheng

引用次数: 0

Dual distal insertions drive pimarane-to-miltiradiene rearrangement with enhanced enzymatic activity. 双远端插入驱动海马兰到米地拉迪尼重排与增强的酶活性。

IF 4.7

生物设计研究(英文) Pub Date : 2025-05-23 eCollection Date: 2025-06-01 DOI: 10.1016/j.bidere.2025.100028

Jianing Liu, Jian Wang, Guanghong Cui, Haiyan Zhang, Mei Tian, Ying Zheng, Baolong Jin, Luqi Huang

{"title":"Dual distal insertions drive pimarane-to-miltiradiene rearrangement with enhanced enzymatic activity.","authors":"Jianing Liu, Jian Wang, Guanghong Cui, Haiyan Zhang, Mei Tian, Ying Zheng, Baolong Jin, Luqi Huang","doi":"10.1016/j.bidere.2025.100028","DOIUrl":"10.1016/j.bidere.2025.100028","url":null,"abstract":"Miltiradiene, the major biosynthetic precursor of abietane diterpenoid natural products, has downstream metabolic derivatives with a significant potential for pharmacologically development. The formation of the characteristic abietane skeleton is attained through the rearrangement of the C13 methyl group in the pimarane intermediate, but the key enzyme mechanism responsible for this rearrangement remains elusive. Previous studies have shown that IrKSL3a in Isodon rubescens generates the pimarane diterpene isopimaradiene, and the insertion of two amino acids in the flexible region distal to the enzyme active center can change the enzyme's function to produce the abietane diterpene miltiradiene. In this paper, mutation studies were conducted on another isopimaradiene synthase IrKSL6 in Isodon rubescens and the miltiradiene synthase SmKSL1 in Salvia miltiorrhiza at these two sites. It was found that the insertion at these two sites is conservative in changing the enzyme function, and it can also affect the solubility of SmKSL1 and its affinity for the substrate. The titer of miltiradiene in the mutant SmKSL1: E550 + KR engineered bacteria increased by approximately 44 % compared to the wild type, the solubility of the protein increased by 24 %, and the catalytic efficiency (Kcat/Km) increased by 26 %. This paper conducted a preliminary study on the influence of the distal flexible region of the protein on the physicochemical properties of the enzyme, establishing critical molecular targets for the rational design of abietane diterpene synthases, while the high-performance mutants obtained provide superior enzymatic components for constructing biosynthesis platforms of pharmacologically relevant metabolites.","PeriodicalId":56832,"journal":{"name":"生物设计研究(英文)","volume":"7 2","pages":"100028"},"PeriodicalIF":4.7,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12710052/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145783612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0