Now Accepting Submissions for Three Special Issues
"Plant BioDesign Hub" -- "Designing Proteins With New Folds and Function" -- "Engineering Microbiomes for Biodesign Applications" -- Submit to a special issue today!Click for details
The open access journal BioDesign Research, published in association with NAU, publishes novel research in the interdisciplinary field of biosystems design.
The editorial board, led by Xiaohan Yang (Oak Ridge National Laboratory) and Alfonso Jaramillo (University of Warwick), is comprised of experts who have made significant and well recognized contributions to the field of biodesign research.
Accepting submissions for three special issues:
• Plant BioDesign Hub (deadlines: Aug 31, 2021; Dec 31, 2022; Mar 31, 2023)
• Designing Proteins With New Folds and Function (deadline: Dec 31, 2022)
• Engineering Microbiomes for Biodesign Applications (deadline: Dec 31, 2022)
Latest ArticlesMore articles
An Overview of Antiviral Peptides and Rational Biodesign Considerations
Viral diseases have contributed significantly to worldwide morbidity and mortality throughout history. Despite the existence of therapeutic treatments for many viral infections, antiviral resistance and the threat posed by novel viruses highlight the need for an increased number of effective therapeutics. In addition to small molecule drugs and biologics, antimicrobial peptides (AMPs) represent an emerging class of potential antiviral therapeutics. While AMPs have traditionally been regarded in the context of their antibacterial activities, many AMPs are now known to be antiviral. These antiviral peptides (AVPs) have been shown to target and perturb viral membrane envelopes and inhibit various stages of the viral life cycle, from preattachment inhibition through viral release from infected host cells. Rational design of AMPs has also proven effective in identifying highly active and specific peptides and can aid in the discovery of lead peptides with high therapeutic selectivity. In this review, we highlight AVPs with strong antiviral activity largely curated from a publicly available AMP database. We then compile the sequences present in our AVP database to generate structural predictions of generic AVP motifs. Finally, we cover the rational design approaches available for AVPs taking into account approaches currently used for the rational design of AMPs.
Activating Silent Glycolysis Bypasses in Escherichia coli
All living organisms share similar reactions within their central metabolism to provide precursors for all essential building blocks and reducing power. To identify whether alternative metabolic routes of glycolysis can operate in E. coli, we complementarily employed in silico design, rational engineering, and adaptive laboratory evolution. First, we used a genome-scale model and identified two potential pathways within the metabolic network of this organism replacing canonical Embden-Meyerhof-Parnas (EMP) glycolysis to convert phosphosugars into organic acids. One of these glycolytic routes proceeds via methylglyoxal and the other via serine biosynthesis and degradation. Then, we implemented both pathways in E. coli strains harboring defective EMP glycolysis. Surprisingly, the pathway via methylglyoxal seemed to immediately operate in a triosephosphate isomerase deletion strain cultivated on glycerol. By contrast, in a phosphoglycerate kinase deletion strain, the overexpression of methylglyoxal synthase was necessary to restore growth of the strain. Furthermore, we engineered the “serine shunt” which converts 3-phosphoglycerate via serine biosynthesis and degradation to pyruvate, bypassing an enolase deletion. Finally, to explore which of these alternatives would emerge by natural selection, we performed an adaptive laboratory evolution study using an enolase deletion strain. Our experiments suggest that the evolved mutants use the serine shunt. Our study reveals the flexible repurposing of metabolic pathways to create new metabolite links and rewire central metabolism.
Design of Protein Segments and Peptides for Binding to Protein Targets
Recent years have witnessed a rise in methods for accurate prediction of structure and design of novel functional proteins. Design of functional protein fragments and peptides occupy a small, albeit unique, space within the general field of protein design. While the smaller size of these peptides allows for more exhaustive computational methods, flexibility in their structure and sparsity of data compared to proteins, as well as presence of noncanonical building blocks, add additional challenges to their design. This review summarizes the current advances in the design of protein fragments and peptides for binding to targets and discusses the challenges in the field, with an eye toward future directions.
Dawn of a New Era for Membrane Protein Design
A major advancement has recently occurred in the ability to predict protein secondary structure from sequence using artificial neural networks. This new accessibility to high-quality predicted structures provides a big opportunity for the protein design community. It is particularly welcome for membrane protein design, where the scarcity of solved structures has been a major limitation of the field for decades. Here, we review the work done to date on the membrane protein design and set out established and emerging tools that can be used to most effectively exploit this new access to structures.
iGEM 2021: A Year in Review
The international Genetically Engineered Machine (iGEM) Foundation has continued to promote synthetic biology education throughout its 2021 competition. The 2021 Virtual iGEM Jamboree was the culmination of the competition’s growth, with 350 projects from 7314 innovators globally. Collegiate, high school, and community lab teams applied their ideas to the Registry of Standard Biological Parts, designing biological systems that provide solutions to an international scope of issues. The environmental, diagnostics, and therapeutics tracks continue to be the most prevalent focal points for projects, as students devise approaches to detrimental impacts of climate change and the COVID-19 pandemic. The competition exemplifies high standards of human practices, biosafety, and biosecurity through responsible biological engineering. As the iGEM Foundation continues pioneering STEM education into the future, equal developments of the competition’s economic accessibility, global diversity, and long-term impact are necessary to allow a larger range of thinkers to access the power of synthetic biology.
What Have We Learned from Design of Function in Large Proteins?
The overarching goal of computational protein design is to gain complete control over protein structure and function. The majority of sophisticated binders and enzymes, however, are large and exhibit diverse and complex folds that defy atomistic design calculations. Encouragingly, recent strategies that combine evolutionary constraints from natural homologs with atomistic calculations have significantly improved design accuracy. In these approaches, evolutionary constraints mitigate the risk from misfolding and aggregation, focusing atomistic design calculations on a small but highly enriched sequence subspace. Such methods have dramatically optimized diverse proteins, including vaccine immunogens, enzymes for sustainable chemistry, and proteins with therapeutic potential. The new generation of deep learning-based ab initio structure predictors can be combined with these methods to extend the scope of protein design, in principle, to any natural protein of known sequence. We envision that protein engineering will come to rely on completely computational methods to efficiently discover and optimize biomolecular activities.