Journal of biotechnology最新文献

{"title":"Employment of light-inducible promoter in genetically engineered cyanobacteria for photosynthetic isobutanol production with simulated diurnal sunlight and CO2","authors":"Meenakshi Das,&nbsp;Soumen K. Maiti","doi":"10.1016/j.jbiotec.2024.07.014","DOIUrl":"10.1016/j.jbiotec.2024.07.014","url":null,"abstract":"<div><p>Cyanobacteria are oxygen-evolving prokaryotes that can be engineered for biofuel production from solar energy, CO_2, and water. Isobutanol (IB) has the potential to serve as an alternative fuel and important chemical feedstock. The research involves engineering <em>Synechocystis</em> sp. PCC 6803, for photosynthetic isobutanol production via the 2-keto-acid pathway and their cultivation in lab-scale photobioreactors. This synthetic pathway involves the heterologous expression of two enzymes, α-ketoisovalerate decarboxylase (Kivd) and alcohol dehydrogenase (Yqhd), under a strong light-inducible promotor, psbA2, known to show increased gene expression under high light. The use of psbA2 could be a valuable strategy for isobutanol production as economic scaling up demands the utilization of natural sunlight, which also provides very high light intensity at midday, facilitating increased production. The study reports isobutanol production from engineered strains containing both pathway genes and with only <em>kivd</em>. In shake flask studies, the highest isobutanol titre of 75 mg L⁻¹ (12th day) was achieved from an engineered strain DM12 under optimized light intensity. DM12 was cultivated in a 2 L flat panel photobioreactor, resulting in a maximum isobutanol titre of 371.8 mg L⁻¹ (10th day) with 2 % CO₂ and 200 μmol photons m⁻² s⁻¹. Cultivation of DM12 in a photobioreactor under mimic diurnal sunlight demonstrated the highest productivity of 39 mg L⁻¹ day⁻¹ with the maximum titre of 308.5 mg L⁻¹ (9th day). This work lays the foundation for sustainable, large-scale biobutanol production using solar energy.</p></div>","PeriodicalId":15153,"journal":{"name":"Journal of biotechnology","volume":"393 ","pages":"Pages 31-40"},"PeriodicalIF":4.1,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141758813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing the amination activity of meso-diaminopimelate dehydrogenase from Symbiobacterium thermophilum by modifying the crucial residue His154 for deamination","authors":"Kehao Yuan ,&nbsp;Zongchao Huo ,&nbsp;Ya`ning Zhang ,&nbsp;Zuran Guo ,&nbsp;Yucan Chang ,&nbsp;Yunming Jin ,&nbsp;Lining Gao ,&nbsp;Tong Zhang ,&nbsp;Yanwei Li ,&nbsp;Qinyuan Ma ,&nbsp;Xiuzhen Gao","doi":"10.1016/j.jbiotec.2024.07.015","DOIUrl":"10.1016/j.jbiotec.2024.07.015","url":null,"abstract":"<div><p>During the deamination and amination processes of <em>meso</em>-diaminopimelate dehydrogenase (<em>meso</em>-DAPDH) from <em>Symbiobacterium thermophilum</em> (StDAPDH), residue R71 was observed to display distinct functions. H154 has been proposed as a basic residue that facilitates water molecules to attack the D-chiral carbon of <em>meso</em>-DAP during deamination. Inspired by the phenomenon of R71, the effects of H154 during deamination and amination were investigated in this study with the goal of enhancing the amination activities of StDAPDH. Single site saturation mutagenesis indicated that almost all of the H154 mutants completely lost their deamination activity towards <em>meso</em>-DAP. However, some H154 variants showed enhanced <em>k</em>_cat/<em>K</em>_m values towards pyruvic acid and other bulky 2-keto acids, such as 2-oxovaleric acid, 4-methyl-2-oxopentanoic acid, 2-ketobutyric acid, and 3-methyl-2-oxobutanoic acid. When combined with the previously reported W121L/H227I mutant, triple mutants with significantly improved <em>k</em>_cat/<em>K</em>_m values (2.4-, 2.5-, 2.5-, and 4.0-fold) towards these 2-keto acids were obtained. Despite previous attempts, mutations at the H154 site did not yield the desired results. Moreover, this study not only recognizes the distinctive impact of H154 on both the deamination and amination reactions, but also provides guidance for further high-throughput screening in protein engineering and understanding the catalytic mechanism of StDAPDH.</p></div>","PeriodicalId":15153,"journal":{"name":"Journal of biotechnology","volume":"393 ","pages":"Pages 1-6"},"PeriodicalIF":4.1,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141734234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sialyllactose supplementation enhances sialylation of Fc-fusion glycoprotein in recombinant Chinese hamster ovary cell culture","authors":"Hoon-Min Lee ,&nbsp;Tae-Ho Kim ,&nbsp;Jong-Ho Park ,&nbsp;Na-Yeong Heo ,&nbsp;Hyun-Seung Kim ,&nbsp;Dae Eung Kim ,&nbsp;Mi Kyeong Lee ,&nbsp;Gyun Min Lee ,&nbsp;Jungmok You ,&nbsp;Yeon-Gu Kim","doi":"10.1016/j.jbiotec.2024.07.016","DOIUrl":"10.1016/j.jbiotec.2024.07.016","url":null,"abstract":"<div><p>Sialylation during <em>N</em>-glycosylation plays an important role in the half-life of therapeutic glycoproteins <em>in vivo</em> and has sparked interest in the production of therapeutic proteins using recombinant Chinese hamster ovary (rCHO) cells. To improve the sialylation of therapeutic proteins, we examined the effect of sialyllactose supplementation on sialylation of Fc-fusion glycoproteins produced in rCHO cells. Two enzymatically-synthesized sialyllactoses, 3′-sialyllactose (3′-SL) and 6′-sialyllactose (6′-SL), were administered separately to two rCHO cell lines producing the same Fc-fusion glycoprotein derived from DUKX-B11 and DG44, respectively. Two sialyllactoses successfully increased sialylation of Fc-fusion glycoprotein in both cell lines, as evidenced by isoform distribution, sialylated <em>N</em>-glycan formation, and sialic acid content. Increased sialylation by adding sialyllactose was likely the result of increased amount of intracellular CMP-sialic acid (CMP-SA), the direct nucleotide sugar for sialylation. Furthermore, the degree of sialylation enhanced by sialyllactoses was slightly effective or nearly similar compared with the addition of <em>N</em>-acetylmannosamine (ManNAc), a representative nucleotide sugar precursor, to increase sialylation of glycoproteins. The effectiveness of sialyllactose was also confirmed using three commercially available CHO cell culture media. Taken together, these results suggest that enzymatically-synthesized sialyllactose represents a promising candidate for culture media supplementation to increase sialylation of glycoproteins in rCHO cell culture.</p></div>","PeriodicalId":15153,"journal":{"name":"Journal of biotechnology","volume":"392 ","pages":"Pages 180-189"},"PeriodicalIF":4.1,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141748307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Porphyromonas gingivalis virulence factors induce toxic effects in SH-SY5Y neuroblastoma cells: GRK5 modulation as a protective strategy","authors":"Daniela Liccardo ,&nbsp;Alessandra Valletta ,&nbsp;Gianrico Spagnuolo ,&nbsp;Caterina Vinciguerra ,&nbsp;Maria Rosaria Lauria ,&nbsp;Alessia Perrotta ,&nbsp;Carmela Del Giudice ,&nbsp;Francesca De Luca ,&nbsp;Giuseppe Rengo ,&nbsp;Sandro Rengo ,&nbsp;Carlo Rengo ,&nbsp;Alessandro Cannavo","doi":"10.1016/j.jbiotec.2024.07.009","DOIUrl":"10.1016/j.jbiotec.2024.07.009","url":null,"abstract":"<div><p>Periodontitis (PDS) is a chronic inflammatory disease initiated by a dysbiosis of oral pathogenic bacterial species, such as Porphyromonas gingivalis (Pg). These bacteria can penetrate the bloodstream, releasing various endo and exotoxins that fuel the infection, and stimulate toxic inflammation in different compartments, including the brain. However, the specific mechanisms by which PDS/Pg contribute to brain disorders, such as Alzheimer’s disease (AD), remain unclear. This study assessed the effects of Pg’s virulence factors - lipopolysaccharide (LPS-Pg) and gingipains (gps) K (Kgp) and Rgp - on SH-SY5Y cells. Our results demonstrated that LPS-Pg activated signaling through the Toll-like receptor (TLR)-2/4 induced a significant downregulation of G protein-coupled receptor kinase 5 (GRK5). Additionally, LPS-Pg stimulation resulted in a robust increase in Tau phosphorylation (pTau) and p53 levels, while causing a marked reduction in Bcl2 and increased cell death compared to unstimulated cells (Ns). LPS-Pg also elevated inducible nitric oxide synthase (iNOS) expression, leading to oxidative damage. In cells overexpressing GRK5 via Adenovirus, LPS-Pg failed to increase iNOS and pTau levels compared to GFP control cells. High GRK5 levels also prevented the nuclear accumulation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB). Furthermore, the overexpression of a GRK5 mutant form lacking the nuclear localization signal (ΔNLS) nearly abolished LPS-Pg induced p53 and iNOS upregulation. Finally, we tested whether Kgp and Rgp mediated similar effects and our data showed that both gps caused a marked downregulation of GRK5 leading to increased p53 and pTau levels.</p><p>In conclusion, this study provides further insight into the toxic effects elicited by Pg in cells and suggests that preventing GRK5 deficiency may be a valid strategy to mitigate Pg-induced toxic effects (i.e. cell death, oxidative damage, and Tau hyperphosphorylation) in SH-SY5Y cells, which are typical molecular hallmarks of neurodegenerative disorders.</p></div>","PeriodicalId":15153,"journal":{"name":"Journal of biotechnology","volume":"393 ","pages":"Pages 7-16"},"PeriodicalIF":4.1,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141734178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxidative refolding by Copper-catalyzed air oxidation consistently increases the homogeneity and activity of a Novel Interleukin-2 mutein","authors":"Sum Lai Lozada ,&nbsp;Jose Alberto Gómez ,&nbsp;Katherine Menéndez ,&nbsp;Tania Gómez ,&nbsp;Daidee Montes de Oca ,&nbsp;Jose L. Durán ,&nbsp;Olga Lidia Fernández ,&nbsp;Yoel Perera ,&nbsp;Gabriela Rivas ,&nbsp;Tammy Boggiano-Ayo ,&nbsp;Nuris Ledon ,&nbsp;Tania Carmenate","doi":"10.1016/j.jbiotec.2024.07.013","DOIUrl":"10.1016/j.jbiotec.2024.07.013","url":null,"abstract":"<div><p>Interleukin-2 (IL-2) has been used in cancer treatment for over 30 years. However, due to its high toxicity, new mutant variants have been developed. These variants retain some of the biological properties of the original molecule but offer other therapeutic advantages. At the Center of Molecular Immunology, the IL-2 no-alpha mutein, an IL-2 agonist with lower toxicity than wtIL-2, has been designed, produced, and is currently being evaluated in a Phase I/II clinical trial. The mutein is produced in <em>E. coli</em> as an insoluble material that must be refolded <em>in vitro</em> to yield a fully active protein. Controlled oxidation steps are essential in the purification process of recombinant proteins produced in <em>E. coli</em> to ensure the proper formation of the disulfide bonds in the molecules. In this case, the new purification process includes a copper-catalyzed air oxidation step to induce disulfide bond establishment. The optimal conditions of pH, copper, protein and detergent concentration for this step were determined through screening. The produced protein demonstrated a conserved 3D structure, higher purity, and greater biological activity than the obtained by established process without the oxidation step. Four batches were produced and evaluated, demonstrating the consistency of the new process.</p></div>","PeriodicalId":15153,"journal":{"name":"Journal of biotechnology","volume":"393 ","pages":"Pages 81-90"},"PeriodicalIF":4.1,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141734235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-density perfusion cultures of the marine bacterium Rhodovulum sulfidophilum for the biomanufacturing of oligonucleotides","authors":"Francesco Iannacci ,&nbsp;João Medeiros Garcia Alcântara ,&nbsp;Martina Marani ,&nbsp;Paolo Camesasca ,&nbsp;Michele Chen ,&nbsp;Fani Sousa ,&nbsp;Massimo Morbidelli ,&nbsp;Mattia Sponchioni","doi":"10.1016/j.jbiotec.2024.07.010","DOIUrl":"10.1016/j.jbiotec.2024.07.010","url":null,"abstract":"<div><p>Therapeutic oligonucleotides (ONs) are typically manufactured via solid-phase synthesis, characterized by limited scalability and huge environmental footprint, limiting their availability. Biomanufactured ONs have the potential to reduce the immunogenic side-effects, and to improve the sustainability of their chemical counterparts. <em>Rhodovulum sulfidophilum</em> was demonstrated a valuable host for the extracellular production of recombinant ONs. However, low viable cell densities and product titer were reported so far. In this work, perfusion cell cultures were established for the intensification of ON biomanufacturing. First, the perfusion conditions were simulated in 50 mL spin tubes, selected as a scale-down model of the process, with the aim of optimizing the medium composition and process parameters. This optimization stage led to an increase in the cell density by 44 % compared to the reference medium formulation. In addition, tests at increasing perfusion rates were conducted until achieving the maximum viable cell density (VCD_max), allowing the determination of the minimum cell-specific perfusion rate (CSPR_min) required to sustain the cell culture. Intriguingly, we discovered in this system also a maximum CSPR, above which growth inhibition starts. By leveraging this process optimization, we show for the first time the conduction of perfusion cultures of <em>R. sulfidophilum</em> in bench-scale bioreactors. This process development pipeline allowed stable cultures for more than 20 days and the continuous biomanufacturing of ONs, testifying the great potential of perfusion processes.</p></div>","PeriodicalId":15153,"journal":{"name":"Journal of biotechnology","volume":"392 ","pages":"Pages 152-160"},"PeriodicalIF":4.1,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0168165624001962/pdfft?md5=b661b5bd1729aa57a79fb7be08d1178e&pid=1-s2.0-S0168165624001962-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141723701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A sustainable bioprocess technology for producing food-flavour (+)-γ-decalactone from castor oil-derived ricinoleic acid using enzymatic activity of Candida parapsilosis: Scale-up optimization and purification using novel composite","authors":"Naziya Syed ,&nbsp;Suman Singh ,&nbsp;Shivani Chaturvedi ,&nbsp;Prashant Kumar ,&nbsp;Deepak Kumar ,&nbsp;Abhinav Jain ,&nbsp;Praveen Kumar Sharma ,&nbsp;Ashween Deepak Nannaware ,&nbsp;Chandan Singh Chanotiya ,&nbsp;Rahul Bhambure ,&nbsp;Pankaj Kumar ,&nbsp;Alok Kalra ,&nbsp;Prasant Kumar Rout","doi":"10.1016/j.jbiotec.2024.07.011","DOIUrl":"10.1016/j.jbiotec.2024.07.011","url":null,"abstract":"<div><p>Ricinoleic acid (RA) from castor oil was employed in biotransformation of peach-flavoured γ-decalactone (GDL), using a <em>Candida parapsilosis</em> strain (MTCC13027) which was isolated from waste of pineapple crown base. Using four variables—pH, cell density, amount of RA, and temperature—the biotransformation parameters were optimized using RSM and BBD. Under optimized conditions (pH 6, 10 % of microbial cells, 10 g/L RA at 28°C), the conversion was maximum and resulted to 80 % (+)-GDL (4.4 g/L/120 h) yield in shake flask (500 mL). Furthermore, optimization was achieved by adjusting the aeration and agitation parameters in a 3 L bioreactor, which were then replicated in a 10 L bioreactor to accurately determine the amount of (+)-GDL. In bioreactor condition, 4.7 g/L (&gt;85 %) of (+)-GDL is produced with 20 % and 40 % dissolved oxygen (1.0 vvm) at 150 rpm in 72 h and 66 h, respectively. Further, a new Al-Mg-Ca-Si composite column-chromatography method is developed to purify enantiospecific (+)-GDL (99.9 %). This (+)-GDL is 100 % nature-identical as validated through ¹⁴C-radio-carbon dating. Thorough chemical investigation of enantiospecific (+)-GDL is authenticated for its use as flavour. This bioflavour has been developed through a cost-effective biotechnological process in response to the demand from the food industry on commercial scale.</p></div>","PeriodicalId":15153,"journal":{"name":"Journal of biotechnology","volume":"393 ","pages":"Pages 17-30"},"PeriodicalIF":4.1,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141691802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimizing bio-vanillin synthesis from ferulic acid via Pediococcus acidilactici: A systematic approach to process enhancement and yield maximization","authors":"Gomathi Subramani,&nbsp;Rameshpathy Manian","doi":"10.1016/j.jbiotec.2024.07.005","DOIUrl":"10.1016/j.jbiotec.2024.07.005","url":null,"abstract":"<div><p>The use of lignocellulosic biomass to create natural flavor has drawn attention from researchers. A key flavoring ingredient that is frequently utilized in the food industry is vanillin. In this present study, <em>Pediococcus acidilactici</em> PA VIT effectively involved in the production of bio-vanillin by using Ferulic acid as an intermediate with a yield of 11.43 µg/mL. The bio-vanillin produced by <em>Pediococcus acidilactici</em> PA VIT was examined using FTIR, XRD, HPLC, and SEM techniques. These characterizations exhibited a unique fingerprinting signature like that of standard vanillin. Additionally, the one variable at a time method, placket Burmann method, and response surface approach, were employed to optimize bio-vanillin. Based on the central composite rotary design, the most important process factors were determined such as agitation speed, substrate concentration, and inoculum size. After optimization, bio-vanillin was found to have tenfold increase, with a maximum yield of 376.4 µg/mL obtained using the response surface approach. The kinetic study was performed to analyze rate of reaction and effect of metal ions in the production of bio-vanillin showing Km of 10.25, and Vmax of 1250 were required for the reaction. The metal ions that enhance the yield of bio-vanillin are Ca²⁺, k⁺, and Mg²⁺ and the metal ions that affects the yield of bio-vanillin are Pb⁺ and Cr⁺ were identified from the effect of metal ions in the bio-vanillin production.</p></div>","PeriodicalId":15153,"journal":{"name":"Journal of biotechnology","volume":"393 ","pages":"Pages 49-60"},"PeriodicalIF":4.1,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141688946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A new synthetic biology system for investigating the biosynthesis of antibiotics and other secondary metabolites in streptomycetes","authors":"Rachel Javorova ,&nbsp;Bronislava Rezuchova ,&nbsp;Lubomira Feckova ,&nbsp;Renata Novakova ,&nbsp;Dominika Csolleiova ,&nbsp;Maria Kopacova ,&nbsp;Vladimir Patoprsty ,&nbsp;Filip Opaterny ,&nbsp;Beatrica Sevcikova ,&nbsp;Jan Kormanec","doi":"10.1016/j.jbiotec.2024.07.007","DOIUrl":"https://doi.org/10.1016/j.jbiotec.2024.07.007","url":null,"abstract":"<div><p>We have created a novel synthetic biology expression system allowing easy refactoring of biosynthetic gene clusters (BGCs) as monocistronic transcriptional units. The system is based on a set of plasmids containing a strong <em>kasOp*</em> promoter, RBS and terminators. It allows the cloning of biosynthetic genes into transcriptional units <em>kasOp</em>*-gene(s)-terminator flanked by several rare restriction cloning sites that can be sequentially combined into the artificial BGC in three compatible <em>Streptomyces</em> integration vectors. They allow a simultaneous integration of these BGCs at three different <em>attB</em> sites in the <em>Streptomyces</em> chromosome. The system was validated with biosynthetic genes from two known BGCs for aromatic polyketides landomycin and mithramycin.</p></div>","PeriodicalId":15153,"journal":{"name":"Journal of biotechnology","volume":"392 ","pages":"Pages 128-138"},"PeriodicalIF":4.1,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141605264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AFP: Finding pathways accounting for stoichiometry along with atom group tracking in metabolic network","authors":"Yiran Huang ,&nbsp;Tao Ma ,&nbsp;Zhiyuan Wan ,&nbsp;Cheng Zhong ,&nbsp;Jianyi Wang","doi":"10.1016/j.jbiotec.2024.07.004","DOIUrl":"10.1016/j.jbiotec.2024.07.004","url":null,"abstract":"<div><p>Automatically finding novel pathways plays an important role in the initial designs of metabolic pathways in synthetic biology and metabolic engineering. Although path-finding methods have been successfully applied in identifying valuable synthetic pathways, few efforts have been made in fusing atom group tracking into building stoichiometry model to search metabolic pathways from arbitrary start compound via Mixed Integer Linear Programming (MILP). We propose a novel method called AFP to find metabolic pathways by incorporating atom group tracking into reaction stoichiometry via MILP. AFP tracks the movements of atom groups in the reaction stoichiometry to construct MILP model to search the pathways containing atom groups exchange in the reactions and adapts the MILP model to provide the options of searching pathways from an arbitrary or given compound to the target compound. Combining atom group tracking with reaction stoichiometry to build MILP model for pathfinding may promote the search of well-designed alternative pathways at the stoichiometric modeling level. The experimental comparisons to the known pathways show that our proposed method AFP is more effective to recover the known pathways than other existing methods and is capable of discovering biochemically feasible pathways producing the metabolites of interest.</p></div>","PeriodicalId":15153,"journal":{"name":"Journal of biotechnology","volume":"392 ","pages":"Pages 139-151"},"PeriodicalIF":4.1,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141620008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}