Biotechnology and Bioengineering最新文献

{"title":"Mesenchymal Stem Cells-Derived Small Extracellular Vesicles and Their Validation as a Promising Treatment for Chondrosarcoma in a 3D Model in Vitro","authors":"Eugenia Romano,&nbsp;Francesca Perut,&nbsp;Sofia Avnet,&nbsp;Gemma Di Pompo,&nbsp;Simona Silvestri,&nbsp;Felicia Roffo,&nbsp;Nicola Baldini,&nbsp;Paolo Antonio Netti,&nbsp;Enza Torino","doi":"10.1002/bit.28909","DOIUrl":"10.1002/bit.28909","url":null,"abstract":"<p>Chondrosarcomas (CHS) constitute approximately 20% of all primary malignant bone tumors, characterized by a slow growth rate with initial manifestation of few signs and symptoms. These malignant cartilaginous neoplasms, particularly those with dedifferentiated histological subtypes, pose significant therapeutic challenges, as they exhibit high resistance to both radiation and chemotherapy. Ranging from relatively benign, low-grade tumors (grade I) to aggressive high-grade tumors with the potential for lung metastases and a grim prognosis, there is a critical need for innovative diagnostic and therapeutic approaches, particularly for patients with more aggressive forms. Herein, small extracellular vesicles (sEVs) derived from mesenchymal stem cells are presented as an efficient nanodelivery tool to enhance drug penetration in an in vitro 3D model of CHS. Employing high-pressure homogenization (HPH), we achieved unprecedented encapsulation efficiency of doxorubicin (DXR) in sEVs derived from mesenchymal stem cells (MSC-EVs). Subsequently, a comparative analysis between free DXR and MSC-EVs encapsulated with DXR (DXR-MSC-EVs) was conducted to assess their penetration and uptake efficacy in the 3D model. The results unveiled a higher incidence of necrotic cells and a more pronounced toxic effect with DXR-MSC-EVs compared to DXR alone. This underscores the remarkable ability of MSC-EVs to deliver drugs in complex environments, highlighting their potential application in the treatment of aggressive CHS.</p>","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"122 3","pages":"667-676"},"PeriodicalIF":3.5,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bit.28909","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142841506","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":"Biosynthesis of Bacteriochlorophylls and Bacteriochlorophyllides in Escherichia coli","authors":"Baiyang Wang,&nbsp;Qiancheng Liao,&nbsp;Chenyang Xia,&nbsp;Fei Gan","doi":"10.1002/bit.28908","DOIUrl":"10.1002/bit.28908","url":null,"abstract":"<div>\u0000 \u0000 <p>Photosynthesis, the most important biological process on Earth, converts light energy into chemical energy with essential pigments like chlorophylls and bacteriochlorophylls. The ability to reconstruct photosynthesis in heterotrophic organisms could significantly impact solar energy utilization and biomass production. In this study, we focused on constructing light-dependent biosynthesis pathways for bacteriochlorophyll (BChl) <i>a</i> and bacteriochlorophyllide (BChlide) <i>d</i> and <i>c</i> in the model strain <i>Escherichia coli</i>. The production of the starting compound, Mg protoporphyrin monomethylester, was optimized by screening the ribosome binding sites for the expression of each of the five genes. By fusing a maltose-binding protein and apolipoprotein A-I domain with the membrane protein BchF, the yield of 3-hydroxyethyl-Chlide <i>a</i> was increased by five-fold. Anaerobic cultivation of the engineered <i>E. coli</i> strains facilitated the reduction of the C7=C8 double bond by chlorophyllide <i>a</i> oxidoreductase, a critical step in BChl <i>a</i> synthesis. We further enhanced BChl <i>a</i> production by adjusting the isopropyl-β-<span>d</span>-thiogalactopyranoside concentration to optimize enzyme production and introducing an exogenous superoxide dismutase to combat oxidative stress. Additionally, fusing BciC with a RIAD tag resulted in an eight-fold increase in the production of 3-vinyl BChlide <i>d</i>. This study lays the foundation for the reconstitution of BChl-based photosynthetic apparatus in heterotrophic model organisms, offering promising avenues for future research and applications in biotechnology.</p></div>","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"122 3","pages":"710-723"},"PeriodicalIF":3.5,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142841814","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":"An Additive-Fabricated Biphasic Scaffold for Procedurally Promoting Bone Regeneration via Antioxidant and Osteogenesis","authors":"Chunyu Han,&nbsp;Zhenxu Wu,&nbsp;Yuqi Gao,&nbsp;Shuang Yang,&nbsp;Yu Wang,&nbsp;Min Guo,&nbsp;Yueyue Li,&nbsp;Wanzhong Yin,&nbsp;Ling Liu,&nbsp;Wenzhi Song,&nbsp;Peibiao Zhang,&nbsp;Liqiang Wang","doi":"10.1002/bit.28896","DOIUrl":"10.1002/bit.28896","url":null,"abstract":"<div>\u0000 \u0000 <p>The repair process of bone tissue includes the early inflammatory response period and the late tissue repair period. It has been widely approved to be beneficial to the repair of bone injury by procedurally inhibiting the inflammatory response in the early stage and promoting bone regeneration in the late stage. In this study, the nano-hydroxyapatite/Poly(glycolide-co-caprolactone) (n-HA/PGCL) scaffold loaded with icariin was fabricated by fused deposition modeling technique, and the quercetin-loaded GelMA was further filled into the scaffold pores via light-curing methods to form a biphasic scaffold loaded with dual molecules (PHI + GQ scaffold). The releases of icariin and quercetin were sequential due to different degradation rates of GelMA and PGCL. In vitro, the scaffold not only scavenged reactive oxygen species production, but also promoted osteogenic differentiation of the MC-3T3-E1 cells. Furthermore, in vivo bone reconstruction of PHI + GQ scaffold was better than other groups by assessment of micro-CT data. In addition, the immunofluorescence staining of Arg-1 and iNOS indicated that PHI + GQ scaffold created an immune microenvironment conducive to bone repair due to the release of quercetin in the early stage, and HE and Masson staining suggested that PHI + GQ scaffold induced more new bone formation. These results demonstrated that the biphasic scaffold loaded with icariin and quercetin had both antioxidants in the early stage and osteogenesis properties in the late stage, obtaining satisfactory bone repair outcomes. Thus, the biphasic scaffold loaded with icariin and quercetin for sequential release could provide a promising solution for the restoration of bone defects and represent a potential strategy for bone regeneration.</p></div>","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"122 3","pages":"654-666"},"PeriodicalIF":3.5,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142832161","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":"3D Printed GelMA/CHIMA Cross-Linked Network Hydrogel for Angiogenesis","authors":"Zixian Liu,&nbsp;Meng Li,&nbsp;Rong Cheng,&nbsp;Lijing Wang,&nbsp;Peiyi Hou,&nbsp;Lu Han,&nbsp;Shengbo Sang","doi":"10.1002/bit.28907","DOIUrl":"10.1002/bit.28907","url":null,"abstract":"<div>\u0000 \u0000 <p>Vascularization is a key issue facing the construction of functional three-dimensional (3D) tissues, which is critical for the long-term survival and stability of tissue construct transplantation. In this study, a photocurable hydrogel material carboxymethyl chitosan (CHIMA) was successfully prepared and integrated with methacryloyl gelatin (GelMA) to construct the bioink GelMA/CHIMA, which was subsequently used 3D printing technology to prepared a bioactive scaffold with angiogenesis-inducing functionality. The results showed that the cross-linked GelMA/CHIMA bioink had a porous structure that supported cell growth and metabolism. The incorporation of CHIMA could significantly improve the hydrophilicity, swelling rate, pressure resistance and mechanical strength of the bioink. GelMA/CHIMA bioink supported the survival and continued proliferation of human umbilical vein endothelial cells (HUVECs) in the scaffold. In particular, the bioink composed of 8 wt% GelMA and 2 wt% CHIMA could stimulate the expression of angiogenesis genes. 3D printed bioactive scaffolds supported the survival of HUVECs and had abundant protein deposition including CD31 and VEGF. Therefore, this study constructed a bioactive scaffold with angiogenesis induction function, which provides a feasible strategy for the construction of vascularized complex tissues.</p></div>","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"122 3","pages":"642-653"},"PeriodicalIF":3.5,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142810139","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":"Biotechnology and Bioengineering: Volume 122, Number 1, January 2025","authors":"","doi":"10.1002/bit.28741","DOIUrl":"10.1002/bit.28741","url":null,"abstract":"","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"122 1","pages":"1-4"},"PeriodicalIF":3.5,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bit.28741","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142804595","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":"Oleaginous Yeast Biology Elucidated With Comparative Transcriptomics","authors":"Sarah J. Weintraub,&nbsp;Zekun Li,&nbsp;Carter L. Nakagawa,&nbsp;Joseph H. Collins,&nbsp;Eric M. Young","doi":"10.1002/bit.28891","DOIUrl":"10.1002/bit.28891","url":null,"abstract":"<div>\u0000 \u0000 <p>Extremophilic yeasts have favorable metabolic and tolerance traits for biomanufacturing- like lipid biosynthesis, flavinogenesis, and halotolerance – yet the connection between these favorable phenotypes and strain genotype is not well understood. To this end, this study compares the phenotypes and gene expression patterns of biotechnologically relevant yeasts <i>Yarrowia lipolytica</i>, <i>Debaryomyces hansenii</i>, and <i>Debaryomyces subglobosus</i> grown under nitrogen starvation, iron starvation, and salt stress. To analyze the large data set across species and conditions, two approaches were used: a “network-first” approach where a generalized metabolic network serves as a scaffold for mapping genes and a “cluster-first” approach where unsupervised machine learning co-expression analysis clusters genes. Both approaches provide insight into strain behavior. The network-first approach corroborates that <i>Yarrowia</i> upregulates lipid biosynthesis during nitrogen starvation and provides new evidence that riboflavin overproduction in <i>Debaryomyces</i> yeasts is overflow metabolism that is routed to flavin cofactor production under salt stress. The cluster-first approach does not rely on annotation; therefore, the coexpression analysis can identify known and novel genes involved in stress responses, mainly transcription factors and transporters. Therefore, this work links the genotype to the phenotype of biotechnologically relevant yeasts and demonstrates the utility of complementary computational approaches to gain insight from transcriptomics data across species and conditions.</p></div>","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"122 3","pages":"677-697"},"PeriodicalIF":3.5,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142804859","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":"Monitoring of the Biotechnological Production of Dihydroxyacetone Using a Low-Field 1H NMR Spectrometer","authors":"Lukas Mahler,&nbsp;Ebru Tasdemir,&nbsp;Anna Nickisch-Hartfiel,&nbsp;Christian Mayer,&nbsp;Martin Jaeger","doi":"10.1002/bit.28901","DOIUrl":"10.1002/bit.28901","url":null,"abstract":"<p>The concept of sustainable production necessitates the utilization of waste and by-products as raw materials, the implementation of biotechnological processes, and the introduction of automated real-time monitoring for efficient use of resources. One example is the biocatalyzed conversion of the reusable by-product glycerin by acetic acid bacteria to dihydroxyacetone (DHA), which is of great importance to the cosmetic industry. The application of compact spectrometers enables the rapid measurement of samples while simultaneously reducing the consumption of resources and energy. Yet, this approach requires comprehensive data preprocessing and, on occasion, multivariate data analysis. For the process monitoring of the production of DHA, a low-field ¹H nuclear magnetic resonance (NMR) spectrometer was implemented in on-line mode. Small-volume samples were taken from a bypass and transferred to the spectrometer by an autosampler. Complete analysis within minutes allowed real-time process control. To this purpose, reliable automated spectral preprocessing preceded the creation of a univariate model. The model enabled the acquisition of process knowledge from chemical kinetics and facilitated the tracking of both substrate and product concentrations, requiring independent calibration. As a second multivariate approach, principal component analysis was utilized to monitor the process in a semi-quantitative manner without the necessity for calibration. The results of this study are beneficial for real-time monitoring applications with the objective of exerting control over the process in question while minimizing expenditure.</p>","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"122 3","pages":"561-569"},"PeriodicalIF":3.5,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bit.28901","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142804863","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":"Fluorescent Reporter-Based Fiber Optic Probe for Continuous Detection of Antibodies","authors":"Suman Nandy,&nbsp;Binh V. Vu,&nbsp;Vijay M. Maranholkar,&nbsp;Atul Goyal,&nbsp;Katerina Kourentzi,&nbsp;Richard C. Willson","doi":"10.1002/bit.28900","DOIUrl":"10.1002/bit.28900","url":null,"abstract":"<div>\u0000 \u0000 <p>Measurement of antibody and antibody fusion protein concentration is vital for process development and manufacturing. Continuous, in-line monitoring of antibody concentration could be useful in a variety of applications, such as controlling the loading of protein A columns to prevent breakthrough, monitoring bioreactor titer, and detecting leaks past ultrafiltration/diafiltration membranes. Molecule-specific monitoring techniques are advantageous for antibody detection in cell culture fluid in the presence of complex process impurities. Here we report a continuous in-line, real-time IgG monitoring platform using a fiber-optic biosensor with a replaceable sensor tip covalently functionalized with a fluor-labeled protein consisting of a pentamer of the Z domain (a more stable form of the B domain) of protein A. The sensor demonstrates concentration-dependent fluorescence enhancement in the presence of human IgG (0.01–0.75 g/L), with consistent signals during five runs each with 1 and 0.1 g/L IgG, and maintains its specificity in the presence of Chinese hamster ovary (CHO) cell culture fluid. A 5% breakthrough of a typical 10 g/L load would be detected in less than 20 s in a flowing stream emerging from a protein A column without prior sample preparation. This sensor platform may be suitable for monitoring IgG and fragment, crystallizable (Fc) fusion proteins in diverse upstream and downstream bioprocess applications.</p>\u0000 </div>","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"122 3","pages":"538-547"},"PeriodicalIF":3.5,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142804860","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":"Increased Mevalonate Production Using Engineered Citrate Synthase and Phosphofructokinase Variants of Escherichia coli","authors":"Jeffrey K. Dodelin,&nbsp;Abigail E. Rose,&nbsp;Hemshikha Rajpurohit,&nbsp;Mark A. Eiteman","doi":"10.1002/bit.28902","DOIUrl":"10.1002/bit.28902","url":null,"abstract":"<p>Mevalonate is a biochemical precursor to a wide range of isoprenoids. The mevalonate pathway uses three moles of acetyl-CoA, and therefore native pathways which metabolize acetyl-CoA compete with mevalonate synthesis. Moreover, the final step in mevalonate formation, mediated by hydroxymethylglutaryl-CoA reductase, requires NADPH as a co-substrate. This study focuses on chromosomal modification of citrate synthase (GltA) involved in acetyl-CoA utilization and phosphofructokinase (PfkA) involved in NADPH formation to increase the yield and productivity of mevalonate in <i>Escherichia coli</i> overexpressing the three genes of the heterologous mevalonate pathway. Nine GltA variants were compared for mevalonate production with the Δ<i>gltA</i> knockout and the wild-type GltA strain in shake flasks in the absence and presence of casamino acids. In the presence of casamino acids, all variants generated mevalonate at a greater yield than the wild-type control, but less than the GltA knockout. In the absence of casamino acids, the strain expressing wild-type GltA generated the greatest yield of mevalonate, while most variants instead accumulated primarily acetate. Using the wild-type strain and two citrate synthase variants, four phosphofructokinase variants were also compared with the Δ<i>pfkA</i> knockout and the wild-type strain, but PfkA variants generated less mevalonate than the corresponding wild-type PfkA strain. Controlled processes at the 1-liter scale comparing five strains demonstrated the inverse relationship between yield and productivity, with the GltA[K167A] variant showing the best balance for the yield (0.20 g/g) and productivity (0.87 g/L h). A nitrogen-limited process using the GltA[K167A] variant generated 36.9 g/L mevalonate in 31 h at a yield of 0.31 g/g. This study demonstrates that GltA variants offer a means to affect intracellular acetyl-CoA pools for the generation of acetyl-CoA derived products and that the acetyl-CoA pool rather than NADPH availability is the important limiting factor for mevalonate production.</p>","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"122 3","pages":"548-560"},"PeriodicalIF":3.5,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bit.28902","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142797530","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":"Photoproduction of Aviation Fuel β-Caryophyllene From the Eukaryotic Green Microalga Chlamydomonas reinhardtii","authors":"Xiaotan Dou,&nbsp;Mengjie Li,&nbsp;Yunlong Ge,&nbsp;Gerui Yin,&nbsp;Xinyu Wang,&nbsp;Song Xue,&nbsp;Baolin Jia,&nbsp;Lihan Zi,&nbsp;Huihui Wan,&nbsp;Yimei Xi,&nbsp;Zhanyou Chi,&nbsp;Fantao Kong","doi":"10.1002/bit.28898","DOIUrl":"10.1002/bit.28898","url":null,"abstract":"<div>\u0000 \u0000 <p>β-caryophyllene is a plant-derived sesquiterpene and is regarded as a promising ingredient for aviation fuels. Microalgae can convert CO₂ into energy-rich bioproducts through photosynthesis, making them potential platforms for the sustainable production of sesquiterpenes. However, heterologous sesquiterpene engineering in microalgae is still in its infancy, and β-caryophyllene production in eukaryotic photosynthetic microorganisms has not been reported. In this study, we succeeded in producing β-caryophyllene in the model eukaryotic microalga <i>Chlamydomonas reinhardtii</i> by heterologously expressing a β-caryophyllene synthase (<i>QHS</i>). Furthermore, overexpressing the key enzyme of the 2-C-methyl-D-erythritol 4-phosphate pathway in the <i>QHS</i>-expressing strain (<i>QHS-DXS-HDR</i>−18) resulted in a 17-fold higher β-caryophyllene production compared to the single expression of <i>QHS</i> (<i>QHS</i>−28). Additionally, when isopentenyl diphosphate isomerase (<i>CrIDI</i>) was overexpressed, the β-caryophyllene production was up to 480.6 μg/L in <i>QHS-DXS-HDR-CrIDI</i>−16 and increased by 1.8-fold compared to the parental strain <i>QHS-DXS-HDR</i>−18. Under photoautotrophic and photomixotrophic conditions in photobioreactors, the β-caryophyllene production in <i>QHS-DXS-HDR-CrIDI</i>−16 reached 854.7 and 1016.8 μg/L, respectively. Noticeably, all the β-caryophyllene-producing strains generated in this study did not exhibit adverse effects on cell growth and photosynthesis activity compared to the untransformed strain. This study demonstrates the first successful attempt to produce β-caryophyllene in the eukaryotic microalga <i>C. reinhardtii</i> and develops a novel strategy for increasing sesquiterpene production in eukaryotic photosynthetic microorganisms.</p></div>","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"122 3","pages":"698-709"},"PeriodicalIF":3.5,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142793561","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}