BioTech最新文献

{"title":"The Use of Biologics for Targeting GPCRs in Metastatic Cancers.","authors":"Cian McBrien, David J O'Connell","doi":"10.3390/biotech14010007","DOIUrl":"10.3390/biotech14010007","url":null,"abstract":"<p><p>A comprehensive review of studies describing the role of G-protein coupled receptor (GPCR) behaviour contributing to metastasis in cancer, and the developments of biotherapeutic drugs towards targeting them, provides a valuable resource toward improving our understanding of the opportunities to effectively target this malignant tumour cell adaptation. Focusing on the five most common metastatic cancers of lung, breast, colorectal, melanoma, and prostate cancer, we highlight well-studied and characterised GPCRs and some less studied receptors that are also implicated in the development of metastatic cancers. Of the approximately 390 GPCRs relevant to therapeutic targeting, as many as 125 of these have been identified to play a role in promoting metastatic disease in these cancer types. GPCR signalling through the well-characterised pathways of chemokine receptors, to emerging data on signalling by orphan receptors, is integral to many aspects of the metastatic phenotype. Despite having detailed information on many receptors and their ligands, there are only thirteen approved therapeutics specifically for metastatic cancer, of which three are small molecules with the remainder including synthetic and non-synthetic peptides or monoclonal antibodies. This review will cover the existing and potential use of monoclonal antibodies, proteins and peptides, and nanobodies in targeting GPCRs for metastatic cancer therapy.</p>","PeriodicalId":34490,"journal":{"name":"BioTech","volume":"14 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843943/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468934","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}

{"title":"Aromatic Amino Acids: Exploring Microalgae as a Potential Biofactory.","authors":"Archana Niraula, Amir Danesh, Natacha Merindol, Fatma Meddeb-Mouelhi, Isabel Desgagné-Penix","doi":"10.3390/biotech14010006","DOIUrl":"10.3390/biotech14010006","url":null,"abstract":"<p><p>In recent times, microalgae have emerged as powerful hosts for biotechnological applications, ranging from the production of lipids and specialized metabolites (SMs) of pharmaceutical interest to biofuels, nutraceutical supplements, and more. SM synthesis through bioengineered pathways relies on the availability of aromatic amino acids (AAAs) as an essential precursor. AAAs, phenylalanine, tyrosine, and tryptophan are also the building blocks of proteins, maintaining the structural and functional integrity of cells. Hence, they are crucial intermediates linking the primary and specialized metabolism. The biosynthesis pathway of AAAs in microbes and plants has been studied for decades, but not much is known about microalgae. The allosteric control present in this pathway has been targeted for metabolic engineering in microbes. This review focuses on the biosynthesis of AAAs in eukaryotic microalgae and engineering techniques for enhanced production. All the putative genes involved in AAA pathways in the model microalgae <i>Chlamydomonas reinhardtii</i> and <i>Phaeodactylum tricornutum</i> are listed in this review.</p>","PeriodicalId":34490,"journal":{"name":"BioTech","volume":"14 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143469468","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}

{"title":"Evaluating TcAs for Use in Biotechnology Applications.","authors":"Cole L Martin, John H Hill, Brian D Wright, Solana R Fernandez, Aubrey L Miller, Karina J Yoon, Suzanne E Lapi, Stephen G Aller","doi":"10.3390/biotech14010005","DOIUrl":"10.3390/biotech14010005","url":null,"abstract":"<p><p>ABC toxin complexes (Tcs) are tripartite complexes that come together to form nano-syringe-like translocation systems. ABC Tcs are often compared with <i>Bacillus thuringiensis</i> (Bt) toxins, and as such, they have been highly studied as a potential novel pesticide to combat growing insect resistance. Moreover, it is possible to substitute the cytotoxic hypervariable region with alternative peptides, which promise potential use as a novel peptide delivery system. These toxins possess the unique ability to form active chimeric holotoxins across species and display the capability to translocate a variety of payloads across membrane bilayers. Additionally, mutagenesis on the linker region and the receptor binding domains (RBDs) show that mutations do not inherently cause a loss of functionality for translocation. For these reasons, Tcs have emerged as an ideal candidate for targeted protein engineering. However, elucidation of the specific function of each RBD in relation to target receptor recognition currently limits the use of a rational design approach with any ABC Tc. Additionally, there is a distinct lack of targeting and biodistribution data for many Tcs among mammals and mammalian cell lines. Here, we outline two separate strategies for modifying the targeting capabilities of the A subunit (TcA) from <i>Xenorhabdus nematophilus</i>, Xn-XptA2. We identify novel structural differences that make Xn-XptA2 different than other characterized TcAs and display the modular capabilities of substituting RBDs from alternative TcAs into the Xn-XptA2 scaffold. Finally, we show the first, to our knowledge, biodistribution data of any TcA in mice.</p>","PeriodicalId":34490,"journal":{"name":"BioTech","volume":"14 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843870/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468447","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}

{"title":"Discovery of Innate Immune Response mRNAs That Are Impacted by Structure-Specific Oral Baker's Yeast Beta Glucan Consumption.","authors":"Brian K McFarlin, John H Curtis, Jakob L Vingren, David W Hill, Elizabeth A Bridgeman","doi":"10.3390/biotech14010004","DOIUrl":"10.3390/biotech14010004","url":null,"abstract":"<p><p>The study of nutritional compounds with the potential to train the innate immune response has implications for human health. The objective of the current study was to discover by what means 6 weeks of oral baker's yeast beta glucan (BYBG) supplementation altered the mRNA expression of genes that reflect innate immune training in the absence of a physical stressor. Nineteen adults were randomly assigned to either a Wellmune^® BYBG or Placebo for 6 weeks. BYBG uniquely altered the expression of 40 mRNAs associated with Dectin-1 and trained innate immunity, the innate immune response, the pathogen-associated (PAMP) and damage-associated molecular pattern (DAMP), and the inflammatory response. The observed changes were classified as immune training rather than immune priming due to the progressive increase in the expression of myeloid immune-associated mRNA. Combined with the findings of previous research, the findings of the present study support the claim that oral BYBG supplementation may be associated with trained innate immunity during resting homeostasis. Further, the key findings associated with BYBG may reflect improved responsiveness to future infection (exogenous) and/or sterile-inflammatory (endogenous) challenge.</p>","PeriodicalId":34490,"journal":{"name":"BioTech","volume":"14 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143025055","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}

{"title":"Impact of <i>GAUT1</i> Gene Knockout on Cell Aggregation in <i>Arabidopsis thaliana</i> Suspension Culture.","authors":"Tatyana A Frankevich, Natalya V Permyakova, Yury V Sidorchuk, Elena V Deineko","doi":"10.3390/biotech14010002","DOIUrl":"10.3390/biotech14010002","url":null,"abstract":"<p><p>The development of efficient producers of recombinant pharmaceuticals based on plant cell suspension cultures is a pressing challenge in modern applied science. A primary limitation of plant cell cultures is their relatively low yield of the target protein. One strategy to enhance culture productivity involves reducing cell aggregation. In order to minimize cell-to-cell adhesion in culture, we used Cas9 endonuclease to knock out the <i>GAUT1</i> gene, which is a key gene of pectin biosynthesis in the genome of <i>Arabidopsis thaliana</i>. The resulting knockouts exhibited altered phenotypes and were unable to form viable plants. The suspension cell culture induced from seedlings bearing a homozygous deletion in the <i>GAUT1</i> gene displayed darker coloration and an increased number of large aggregates compared to the control. The biomass accumulation rate showed no difference from the control, while the level of recombinant GFP protein accumulation was significantly reduced. Thus, our findings indicate that disruptions in pectin synthesis and the formation of larger aggregates in the suspension cell culture adversely affect the accumulation of the target recombinant protein. Alternative targets should be sought to reduce cell aggregation levels in plant cell cultures through genome editing.</p>","PeriodicalId":34490,"journal":{"name":"BioTech","volume":"14 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755664/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143025056","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}

{"title":"Current Approaches for Genetic Manipulation of <i>Streptomyces</i> spp.-Key Bacteria for Biotechnology and Environment.","authors":"Sergii Krysenko","doi":"10.3390/biotech14010003","DOIUrl":"10.3390/biotech14010003","url":null,"abstract":"<p><p>Organisms from the genus <i>Streptomyces</i> feature actinobacteria with complex developmental cycles and a great ability to produce a variety of natural products. These soil bacteria produce more than 2/3 of antibiotics used in medicine, and a large variety of bioactive compounds for industrial, medical and agricultural use. Although <i>Streptomyces</i> spp. have been studied for decades, the engineering of these bacteria remains challenging, and the available genetic tools are rather limited. Furthermore, most biosynthetic gene clusters in these bacteria are silent and require strategies to activate them and exploit their production potential. In order to explore, understand and manipulate the capabilities of <i>Streptomyces</i> spp. as a key bacterial for biotechnology, synthetic biology strategies emerged as a valuable component of <i>Streptomyces</i> research. Recent advancements in strategies for genetic manipulation of <i>Streptomyces</i> involving proposals of a large variety of synthetic components for the genetic toolbox, as well as new approaches for genome mining, assembly of genetic constructs and their delivery into the cell, allowed facilitation of the turnaround time of strain engineering and efficient production of new natural products at an industrial scale, but still have strain- and design-dependent limitations. A new perspective offered recently by technical advances in DNA sequencing, analysis and editing proposed strategies to overcome strain- and construct-specific difficulties in the engineering of <i>Streptomyces</i>. In this review, challenges and recent developments of approaches for <i>Streptomyces</i> engineering are discussed, an overview of novel synthetic biology strategies is provided and examples of successful application of new technologies in molecular genetic engineering of <i>Streptomyces</i> are highlighted.</p>","PeriodicalId":34490,"journal":{"name":"BioTech","volume":"14 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755657/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143025135","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}

{"title":"Peptide Inhibitor Assay for Allocating Functionally Important Accessible Sites Throughout a Protein Chain: Restriction Endonuclease EcoRI as a Model Protein System.","authors":"Joji M Otaki","doi":"10.3390/biotech14010001","DOIUrl":"10.3390/biotech14010001","url":null,"abstract":"<p><p>Functionally important amino acid sequences in proteins are often located at multiple sites. Three-dimensional structural analysis and site-directed mutagenesis may be performed to allocate functional sites for understanding structure‒function relationships and for developing novel inhibitory drugs. However, such methods are too demanding to comprehensively cover potential functional sites throughout a protein chain. Here, a peptide inhibitor assay (PIA) was devised to allocate functionally important accessible sites in proteins. This simple method presumes that protein‒ligand interactions, intramolecular interactions, and dimerization interactions can be partially inhibited by high concentrations of competitive \"endogenous\" peptides of the protein of interest. Focusing on the restriction endonuclease EcoRI as a model protein system, many endogenous peptides (6mer-14mer) were synthesized, covering the entire EcoRI protein chain. Some of them were highly inhibitory, but interestingly, the nine most effective peptides were located outside the active sites, with the exception of one. Relatively long peptides with aromatic residues (F, H, W, and Y) corresponding to secondary structures were generally effective. Because synthetic peptides are flexible enough to change length and amino acid residues, this method may be useful for quickly and comprehensively understanding structure‒function relationships and developing novel drugs or epitopes for neutralizing antibodies.</p>","PeriodicalId":34490,"journal":{"name":"BioTech","volume":"14 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755562/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143025134","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}

{"title":"The Effects of the Combined Co-Expression of GroEL/ES and Trigger Factor Chaperones on Orthopoxvirus Phospholipase F13 Production in <i>E. coli</i>.","authors":"Iuliia A Merkuleva, Vladimir N Nikitin, Tatyana D Belaya, Egor A Mustaev, Dmitriy N Shcherbakov","doi":"10.3390/biotech13040057","DOIUrl":"10.3390/biotech13040057","url":null,"abstract":"<p><p>Heterologous protein expression often faces significant challenges, particularly when the target protein has posttranslational modifications, is toxic, or is prone to misfolding. These issues can result in low expression levels, aggregation, or even cell death. Such problems are exemplified by the expression of phospholipase p37, a critical target for chemotherapeutic drugs against pathogenic human orthopoxviruses, including monkeypox and smallpox viruses. The complex structure and broad enzymatic activity of phospholipase p37 render it toxic to host cells, necessitating specialized strategies for heterologous expression. In our study, we addressed these challenges using the vaccinia virus F13 protein as a model. We demonstrated that p37 can be effectively synthesized in <i>E. coli</i> as a GST fusion protein by co-expressing it with the GroEL/ES chaperone system and Trigger Factor chaperone.</p>","PeriodicalId":34490,"journal":{"name":"BioTech","volume":"13 4","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11674265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142898711","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}

{"title":"A Study on the Function of Arginine in the Growth, Immunity, Antioxidant Activity, and Oxygen Carrying-Capacity of Juvenile Gibel Carp (<i>Carassius auratus gibelio</i>).","authors":"Yuqun Li, Lu Zhang, Mingchun Ren, Hualiang Liang, Haifeng Mi, Dongyu Huang","doi":"10.3390/biotech13040056","DOIUrl":"10.3390/biotech13040056","url":null,"abstract":"<p><p>An eight-week trial was designed to study the effects of arginine (Arg) supplemented diets on the growth, immunity, antioxidant activity, and oxygen-carrying capacity of juvenile Gibel carp (<i>Carassius auratus gibelio</i>). A total of 300 fish (27.53 ± 0.03 g) were randomized into 15 equal groups and fed on diets with graded Arg levels: 0 (control), 0.2%, 0.4%, 0.6%, and 0.8% (<i>w</i>/<i>w</i>). The results showed that final body weight (FBW), weight gain rate (WGR), and specific growth rate (SGR) all increased and then declined with increasing levels of Arg supplementation, while feed conversion ratio (FCR) showed the opposite trend. In addition, the fish's whole-body crude protein and ash content had no remarkable difference at different levels of Arg addition (<i>p</i> > 0.05). Supplementation with 0.6% and 0.8% Arg significantly increased plasma alanine transaminase (ALT) activity (<i>p</i> < 0.05). The malondialdehyde (MDA) levels and superoxide dismutase (SOD) activities of the liver were not significantly different between the different levels of Arg supplementation (<i>p</i> > 0.05), while catalase (CAT) activity was significantly increased with 0.4% Arg supplementation levels (<i>p</i> < 0.05). The 0.8% Arg supplementation greatly increased the expression of hepatic-related genes to the Nrf2 signaling pathway, including <i>sod</i> and <i>gpx</i> (<i>p</i> < 0.05). However, the 0.8% Arg supplementation did not significantly increase the relative expression of genes related to the NF-κB signaling pathway, including <i>il-1β</i>, <i>il-8</i>, and <i>tnf-α</i> (<i>p</i> > 0.05). Similarly, the relative expression of hif-1 signaling pathway-related genes at 0.8% Arg supplementation was significantly elevated, including <i>hif-1α</i>, <i>epo</i>, and <i>vegf</i> (<i>p</i> < 0.05). Hence, Arg supplementation could promote growth and improve immune, antioxidant, and oxygen-carrying capacity in juvenile Gibel carp.</p>","PeriodicalId":34490,"journal":{"name":"BioTech","volume":"13 4","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11675026/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142898700","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}

{"title":"Bioenergy Production from Sorghum Distillers Grains via Dark Fermentation.","authors":"Ching-Chun Lu, Chiu-Yue Lin","doi":"10.3390/biotech13040055","DOIUrl":"10.3390/biotech13040055","url":null,"abstract":"<p><p>Sorghum distillers grains (SDGs) produced from a sorghum liquor company were used for generating biohydrogen via dark fermentation at pH 4.5-6.5 and 55 °C with a batch test, and the biohydrogen electricity generation potential was evaluated. The experimental results show that pH markedly affects hydrogen concentration, hydrogen production rate (HPR) and hydrogen yield (HY), in that high acidic pH values result in high values. The HPR and HY ranged from 0.76 to 3.2 L/L-d and 21.4 to 62.3 mL/g chemical oxygen demand, respectively. These hydrogen production values were used to evaluate bioelectricity generation using a newly developed gas/liquid-fuel engine. The results show a new and prospective biomass source for biohydrogen production, bioelectricity generation and simultaneously solving the problem of treating SDGs when producing kaoliang liquor. Applications of the experimental results are also discussed.</p>","PeriodicalId":34490,"journal":{"name":"BioTech","volume":"13 4","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11674095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142898701","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}