scholarly journals Directed Evolution of Therapeutic Antibodies Targeting Glycosylation in Cancer

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2824
Author(s):  
Ron Amon ◽  
Ronit Rosenfeld ◽  
Shahar Perlmutter ◽  
Oliver C. Grant ◽  
Sharon Yehuda ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Therapeutic Efficacy ◽  
Surface Display ◽  
Yeast Surface Display ◽  
Structural Basis ◽  
Therapeutic Antibodies ◽  
Pancreatic Cancers ◽  
Yeast Surface ◽  
Directed Molecular Evolution ◽  
Cancer Theranostics

Glycosylation patterns commonly change in cancer, resulting in expression of tumor-associated carbohydrate antigens (TACA). While promising, currently available anti-glycan antibodies are not useful for clinical cancer therapy. Here, we show that potent anti-glycan antibodies can be engineered to acquire cancer therapeutic efficacy. We designed yeast surface display to generate and select for therapeutic antibodies against the TACA SLea (CA19−9) in colon and pancreatic cancers. Elite clones showed increased affinity, better specificity, improved binding of human pancreatic and colon cancer cell lines, and increased complement-dependent therapeutic efficacy. Molecular modeling explained the structural basis for improved antibody functionality at the molecular level. These new tools of directed molecular evolution and selection for effective anti-glycan antibodies, provide insights into the mechanisms of cancer therapy targeting glycosylation, and provide major methodological advances that are likely to open up innovative avenues of research in the field of cancer theranostics.

scholarly journals Development and Characterization of Two Types of Surface Displayed Levansucrases for Levan Biosynthesis

Catalysts ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 757
Author(s):  
Huiyi Shang ◽  
Danni Yang ◽  
Dairong Qiao ◽  
Hui Xu ◽  
Yi Cao
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Molecular Weight ◽  
Large Scale ◽  
Surface Display ◽  
Yeast Surface Display ◽  
Fusion Partner ◽  
Whole Cell ◽  
Food Industries ◽  
Yeast Surface ◽  
The Stability

Levan has wide applications in chemical, cosmetic, pharmaceutical and food industries. The free levansucrase is usually used in the biosynthesis of levan, but the poor reusability and low stability of free levansucrase have limited its large-scale use. To address this problem, the surface-displayed levansucrase in Saccharomyces cerevisiae were generated and evaluated in this study. The levansucrase from Zymomonas mobilis was displayed on the cell surface of Saccharomyces cerevisiae EBY100 using a various yeast surface display platform. The N-terminal fusion partner is based on a-agglutinin, and the C-terminal one is Flo1p. The yield of levan produced by these two whole-cell biocatalysts reaches 26 g/L and 34 g/L in 24 h, respectively. Meanwhile, the stability of the surface-displayed levansucrases is significantly enhanced. After six reuses, these two biocatalysts retained over 50% and 60% of their initial activities, respectively. Furthermore, the molecular weight and polydispersity test of the products suggested that the whole-cell biocatalyst of levansucrase displayed by Flo1p has more potentials in the production of levan with low molecular weight which is critical in certain applications. In conclusion, our method not only enable the possibility to reuse the enzyme, but also improves the stability of the enzyme.

scholarly journals The Role of Yeast-Surface-Display Techniques in Creating Biocatalysts for Consolidated BioProcessing

Catalysts ◽  
2018 ◽  
Vol 8 (3) ◽  
pp. 94 ◽  
Author(s):  
Ian Dominic Flormata Tabañag ◽  
I-Ming Chu ◽  
Yu-Hong Wei ◽  
Shen-Long Tsai
Keyword(s):  
Climate Change ◽  
Lignocellulosic Biomass ◽  
Surface Engineering ◽  
Consolidated Bioprocessing ◽  
Surface Display ◽  
Yeast Surface Display ◽  
Qualitative Assessment ◽  
The Status ◽  
Yeast Surface

Climate change is directly linked to the rapid depletion of our non-renewable fossil resources and has posed concerns on sustainability. Thus, imploring the need for us to shift from our fossil based economy to a sustainable bioeconomy centered on biomass utilization. The efficient bioconversion of lignocellulosic biomass (an ideal feedstock) to a platform chemical, such as bioethanol, can be achieved via the consolidated bioprocessing technology, termed yeast surface engineering, to produce yeasts that are capable of this feat. This approach has various strategies that involve the display of enzymes on the surface of yeast to degrade the lignocellulosic biomass, then metabolically convert the degraded sugars directly into ethanol, thus elevating the status of yeast from an immobilization material to a whole-cell biocatalyst. The performance of the engineered strains developed from these strategies are presented, visualized, and compared in this article to highlight the role of this technology in moving forward to our quest against climate change. Furthermore, the qualitative assessment synthesized in this work can serve as a reference material on addressing the areas of improvement of the field and on assessing the capability and potential of the different yeast surface display strategies on the efficient degradation, utilization, and ethanol production from lignocellulosic biomass.

scholarly journals Synthetic repertoires derived from convalescent COVID-19 patients enable discovery of SARS-CoV-2 neutralizing antibodies and a novel quaternary binding modality

2021 ◽  
Author(s):  
Jimmy D Gollihar ◽  
Jason S McLellan ◽  
Daniel R Boutz ◽  
Jule Goike ◽  
Andrew Horton ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Surface Display ◽  
Functional Characterization ◽  
Yeast Surface Display ◽  
Spike Protein ◽  
Emerging Pathogens ◽  
Effective Interventions ◽  
Yeast Surface

The ongoing evolution of SARS-CoV-2 into more easily transmissible and infectious variants has sparked concern over the continued effectiveness of existing therapeutic antibodies and vaccines. Hence, together with increased genomic surveillance, methods to rapidly develop and assess effective interventions are critically needed. Here we report the discovery of SARS-CoV-2 neutralizing antibodies isolated from COVID-19 patients using a high-throughput platform. Antibodies were identified from unpaired donor B-cell and serum repertoires using yeast surface display, proteomics, and public light chain screening. Cryo-EM and functional characterization of the antibodies identified N3-1, an antibody that binds avidly (Kd,app = 68 pM) to the receptor binding domain (RBD) of the spike protein and robustly neutralizes the virus in vitro. This antibody likely binds all three RBDs of the trimeric spike protein with a single IgG. Importantly, N3-1 equivalently binds spike proteins from emerging SARS-CoV-2 variants of concern, neutralizes UK variant B.1.1.7, and binds SARS-CoV spike with nanomolar affinity. Taken together, the strategies described herein will prove broadly applicable in interrogating adaptive immunity and developing rapid response biological countermeasures to emerging pathogens.

Characterization, performance, and applications of a yeast surface display-based biocatalyst

RSC Advances ◽  
2015 ◽  
Vol 5 (25) ◽  
pp. 19166-19175 ◽  
Author(s):  
J. M. Eby ◽  
S. W. Peretti
Keyword(s):  
Cost Analysis ◽  
Copy Number ◽  
Surface Display ◽  
Hydrolytic Activity ◽  
Yeast Surface Display ◽  
Expression Level ◽  
Yeast Surface ◽  
Commercial Lipase

Yeast surface display (YSD) of two lipases. Measured expression level and copy number. Synthetic and hydrolytic activity comparable to commercial lipase. Cost analysis of YSD system vs. commercial formulations.

Engineering Antibody Affinity by Yeast Surface Display

2004 ◽  
pp. 348-358 ◽  
Author(s):  
David W Colby ◽  
Brenda A Kellogg ◽  
Christilyn P Graff ◽  
Yik A Yeung ◽  
Jeffrey S Swers ◽  
...  
Keyword(s):  
Surface Display ◽  
Yeast Surface Display ◽  
Antibody Affinity ◽  
Yeast Surface
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