Article
Chemistry, Multidisciplinary
Menghua Wang, Katherine S. Ryan
Summary: In this study, two new l-Alanosine-producing strains were discovered through genome mining. These strains lack the aspartate-nitrosuccinate pathway genes found in the original producer and use a unique set of nitrate-nitrite reductases to reduce nitrate instead. The repurposing of enzymes from the nitrogen cycle for specialized metabolite biosynthesis and the potential for the discovery of new nitric-oxide-derived natural products are demonstrated.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Biotechnology & Applied Microbiology
Zhihui Chen, Yongzhi He, Xinyu Wu, Li Wang, Zhiyang Dong, Xiuzhen Chen
Summary: Through genetic engineering, genes from Trichoderma reesei and N. crassa were successfully transferred to E. coli, enabling efficient synthesis of ergothioneine. The combination of genes from T. reesei showed the best synthesis efficiency, reaching up to 4.34 g/L per liter.
MICROBIAL CELL FACTORIES
(2022)
Article
Chemistry, Multidisciplinary
Sakuntala Mutyala, Shuwei Li, Himanshu Khandelwal, Da Seul Kong, Jung Rae Kim
Summary: This study found that acetate can be converted to succinate under microaerobic conditions by overexpressing citrate synthase (gltA) in Pseudomonas putida. The gltA-KT strain showed a nearly 50% improvement in succinate production compared to the wild type. Under optimal pH of 7.5, the accumulation of succinate was approximately 400% higher than that of the wild type. Overall, gltA overexpression alone resulted in 9.5% of the maximum theoretical yield in a minimal medium with acetate as the sole carbon source. This highlights the importance of citrate synthase in acetate conversion to succinate by P. putida under microaerobic conditions.
Article
Biochemistry & Molecular Biology
Shuai Liu, Bing-Bing Wang, Jian-Zhong Xu, Wei-Guo Zhang
Summary: This study improved the production of L-tryptophan by metabolic engineering, optimizing the shikimate pathway and L-tryptophan branch. The resulting strain produced 53.65 g/L of L-tryptophan, with a yield of 0.238 g/g glucose, setting the basis for the development of other valuable aromatic compounds or derivatives.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Agricultural Engineering
Zhifei Liu, Mengmeng Cai, Siquan Zhou, Jiajia You, Zhenqiang Zhao, Zuyi Liu, Meijuan Xu, Zhiming Rao
Summary: This study successfully increased the production and productivity of L-homoserine by reengineering the metabolic pathway and cell division. The strategies used in this study could be applied to constructing cell factories for producing other L-aspartate derivatives.
BIORESOURCE TECHNOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Shuai Jiang, Dehu Wang, Ruirui Wang, Chunguang Zhao, Qian Ma, Heyun Wu, Xixian Xie
Summary: This study successfully constructed a microbial cell factory for high-level L-citrulline production, achieving the highest reported values through a combination of rational module engineering strategies and dynamic regulation strategies.
METABOLIC ENGINEERING
(2021)
Article
Biotechnology & Applied Microbiology
Shuaiwen Wang, Yu Fang, Zhen Wang, Shuyan Zhang, Liangjia Wang, Yong Guo, Xiaoyuan Wang
Summary: In this study, the impact of ProP, ProVWX, and betABIT on l-threonine production in E. coli was investigated. Deletion of proP or/and proVWX significantly increased l-threonine production, while deletion of betABIT slightly decreased l-threonine production. Deleting either crr or ptsG from the resulting strain further improved l-threonine production, with a productivity increase of 116% compared to the control strain TWF001.
MICROBIAL CELL FACTORIES
(2021)
Article
Biochemical Research Methods
Michael Cotner, Jixun Zhan, Zhen Zhang
Summary: A new probabilistic computational model was constructed to optimize the microbial production of resveratrol in Escherichia coli. By identifying the limiting enzyme and informing the effects of changes in enzyme concentration and source, the model successfully increased the yield of resveratrol in the laboratory system.
ACS SYNTHETIC BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Abinaya Badri, Asher Williams, Adeola Awofiranye, Payel Datta, Ke Xia, Wenqin He, Keith Fraser, Jonathan S. Dordick, Robert J. Linhardt, Mattheos A. G. Koffas
Summary: This study demonstrates the development of single microbial cell factories capable of one-step biosynthesis of chondroitin sulfate (CS) by engineering E. coli, achieving intracellular CS production with high sulfation levels. This marks an important step in animal-free production of sulfated GAGs.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Matthew R. Volpe, Jose A. Velilla, Martin Daniel-Ivad, Jenny J. Yao, Alessia Stornetta, Peter W. Villalta, Hsin-Che Huang, Daniel A. Bachovchin, Silvia Balbo, Rachelle Gaudet, Emily P. Balskus
Summary: In this study, small molecule boronic acid inhibitors were developed to inhibit the biosynthesis of the human gut bacterial genotoxin colibactin. These inhibitors effectively block the genotoxic effects of colibactin on eukaryotic cells by engaging with the peptidase ClbP. The availability of these inhibitors allows for precise control over colibactin production, enabling further study of its contributions to colorectal cancer.
NATURE CHEMICAL BIOLOGY
(2023)
Article
Agriculture, Multidisciplinary
Jie Cheng, Juan Li, Linggang Zheng
Summary: 1,4-Butanediol is a significant commodity chemical currently produced through energy-intensive processes with severe environmental impacts. As market demand increases, attention has shifted towards sustainable bioproduction methods, leading to advancements in metabolic engineering strategies.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2021)
Article
Biotechnology & Applied Microbiology
Mengzhen Nie, Jingyu Wang, Kechun Zhang
Summary: A novel approach was developed to achieve high-yield production of L-arginine from N-acetylglutamate in E. coli by genetically modifying the bacteria and overexpressing specific genes. Co-production of pyruvate and L-arginine was also demonstrated to increase the utilization of input carbon sources.
MICROBIAL CELL FACTORIES
(2023)
Article
Biotechnology & Applied Microbiology
Jae Ho Shin, Aaron John Christian Andersen, Puck Achterberg, Lisbeth Olsson
Summary: In this study, the reverse beta-oxidation pathway was successfully implemented in Corynebacterium glutamicum for production of adipic acid. Despite a small quantity, the presence of adipic acid in the cultivation broth indicated expression and functionality of the synthetic genes. Furthermore, 2,3-dehydroadipyl-CoA hydratase and beta-ketoadipyl-CoA thiolase were identified as potential targets for further improvement of the pathway.
MICROBIAL CELL FACTORIES
(2021)
Article
Biology
Annette R. Rowe, Farshid Salimijazi, Leah Trutschel, Joshua Sackett, Oluwakemi Adesina, Isao Anzai, Liat H. Kugelmass, Michael H. Baym, Buz Barstow
Summary: Extracellular electron transfer (EET) enables microbial electron uptake for the synthesis of complex organic molecules, but there are significant gaps in understanding the mechanism and genetics of electron uptake.
COMMUNICATIONS BIOLOGY
(2021)
Article
Agriculture, Multidisciplinary
Wen Li, Yingying Zhu, Li Wan, Cuie Guang, Wanmeng Mu
Summary: In this study, the de novo and salvage pathways for GDP-fucose synthesis were engineered and optimized in E. coli, leading to increased 2'-FL production. By fine-tuning the expression of related genes, along with the introduction of fucT2 gene, the final engineered strains produced 2.62 and 14.1 g/L of 2'-FL in shake-flask and fed-batch cultivations, respectively.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Julia Fernandez de Luco, Gaston Prez, Bruno Hernandez Cravero, Diego de Mendoza, Guillermo R. Labadie
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2019)
Review
Parasitology
Claudio A. Pereira, Melisa Saye, Chantal Reigada, Ariel M. Silber, Guillermo R. Labadie, Mariana R. Miranda, Edward Valera-Vera
Article
Chemistry, Multidisciplinary
Pamela S. Forastieri, Liliana E. Luna, Raquel M. Cravero, Guillermo R. Labadie
Article
Chemistry, Medicinal
Noelia S. Medran, Melisa Saye, Claudio A. Pereira, Babu L. Tekwani, Agustina La-Venia, Guillermo R. Labadie
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2020)
Article
Biotechnology & Applied Microbiology
C. M. Jimenez, H. L. Alvarez, M. S. Ballari, G. R. Labadie, C. A. N. Catalan, R. E. Toso, D. A. Sampietro
Summary: The study found that cycloartenol and 24-methylenecycloartanol extracted from aerial parts of Euphorbia species can inhibit the growth and mycotoxin production of Fusarium species, and when combined with potassium sorbate, they are more effective in reducing mycotoxin accumulation. This suggests that the mixtures offer a lower mycotoxigenic risk compared to potassium sorbate alone for controlling Fusarium species.
JOURNAL OF APPLIED MICROBIOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Lucia Fargnoli, Esteban A. Panozzo-Zenere, Lucas Pagura, Maria Julia Barison, Julia A. Cricco, Ariel M. Silber, Guillermo R. Labadie
FRONTIERS IN CHEMISTRY
(2020)
Article
Chemistry, Medicinal
Diego G. Ghiano, Alejandro Recio-Balsells, Ana Bortolotti, Lucas A. Defelipe, Adrian Turjanski, Hector R. Morbidoni, Guillermo R. Labadie
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2020)
Article
Chemistry, Medicinal
Exequiel O. J. Porta, Maria Sol Ballari, Renzo Carlucci, Shane Wilkinson, Guoyi Ma, Babu L. Tekwani, Guillermo R. Labadie
Summary: A series of 1,2,3-triazolylsterols were synthesized and evaluated for their activities against the parasites causing neglected tropical diseases. Most of the compounds showed high selectivity and activity against Leishmania donovani, Trypanosoma cruzi, and Trypanosoma brucei. In silico analysis of physicochemical properties was performed to explain the observed activities. The analogs with selective or broad-spectrum antiparasitic activities may be potential candidates for the development of new drugs.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Maria Sol Ballari, Exequiel O. J. Porta, Evelyn Arel Zalazar, Carla M. Borini Etichetti, Jose M. Padron, Javier E. Girardini, Guillermo R. Labadie
Summary: This study evaluated the antiproliferative activity of a series of lipophilic thioether modified salirasib analogues, and found that analogues with three or more isoprene units or a long aliphatic chain exhibited the most potent activity. Furthermore, three analogues with specific antimigratory activity were identified, providing interesting starting points for the development of new antimetastatic agents.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Renzo Carlucci, Maria-Natalia Lisa, Guillermo R. Labadie
Summary: This study demonstrates the diverse noncovalent interactions between the 1,2,3-triazole scaffold and amino acids in proteins, which contribute to protein-ligand binding and may have implications for drug development.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Organic
Miguel Villarreal-Parra, Gabriel E. Di Gresia, Guillermo R. Labadie, Margarita M. Vallejos
Summary: The mechanisms of the asigmatropic and prototropic reactions in the Banert cascade were investigated using density functional theory, quantum theory of atoms in molecules, and natural bond orbital approaches. The calculated energy barriers were consistent with experimental data. The distribution of electron density on transition structures reflected the behavior of reactants in the Banert cascade. The conjugative effects and charge accumulation at the C(3) atom of propargylic azides were found to be related to the activation energies of sigmatropic and prototropic reactions, respectively. These results allow for the prediction of reaction course by evaluating reactants.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Renzo Carlucci, Gabriel Di Gresia, Maria Gabriela Mediavilla, Julia A. A. Cricco, Babu L. L. Tekwani, Shabana I. I. Khan, Guillermo R. R. Labadie
Summary: We synthesized a series of prenyl-1,2,3-triazoles from isoprenyl azides and alkynes to discover new antimalarial drug candidates. Thirteen analogs showed antimalarial activity, with compounds 1o and 1r identified as the most promising leads. The chemoinformatic analysis evaluated physicochemical parameters and cytotoxicity risk, and a potential target for the antimalarial activity was suggested.
RSC MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Julia Fernandez de Luco, Alejandro Recio-Balsells, Diego G. Ghiano, Ana Bortolotti, Juan Manuel Belardinelli, Nina Liu, Pascal Hoffmann, Christian Lherbet, Peter J. Tonge, Babu Tekwani, Hector R. Morbidoni, Guillermo R. Labadie
Summary: Triclosan and isoniazid, known antitubercular compounds, were tested for their leishmanicidal activity using a collection of 37 diverse 1,2,3-triazoles. While some analogs showed activity against Leishmania donovani, there were scarce active compounds against M. tuberculosis. One derivative, 5f, could be a valuable starting point for future antileishmanial drug development, and further investigation is needed to validate a putative leishmanial InhA orthologue as a therapeutic target.
RSC MEDICINAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Jose R. Soberon, Melina A. Sgariglia, Jose A. Carabajal Torrez, Franco A. Aguilar, Edgardo J. Pero, Diego A. Sampietro, Julia Fernandez de Luco, Guillermo R. Labadie
Article
Chemistry, Multidisciplinary
Margarita M. Vallejos, Guillermo R. Labadie