Biological and Molecular Components for Genetically Engineering Biosensors in PlantsRead the full article
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.
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High-Throughput Prediction and Design of Novel Conopeptides for Biomedical Research and Development
Cone snail venoms have been considered a valuable treasure for international scientists and businessmen, mainly due to their pharmacological applications in development of marine drugs for treatment of various human diseases. To date, around 800 Conus species are recorded, and each of them produces over 1,000 venom peptides (termed as conopeptides or conotoxins). This reflects the high diversity and complexity of cone snails, although most of their venoms are still uncharacterized. Advanced multiomics (such as genomics, transcriptomics, and proteomics) approaches have been recently developed to mine diverse Conus venom samples, with the main aim to predict and identify potentially interesting conopeptides in an efficient way. Some bioinformatics techniques have been applied to predict and design novel conopeptide sequences, related targets, and their binding modes. This review provides an overview of current knowledge on the high diversity of conopeptides and multiomics advances in high-throughput prediction of novel conopeptide sequences, as well as molecular modeling and design of potential drugs based on the predicted or validated interactions between these toxins and their molecular targets.
Revealing CO2-Fixing SAR11 Bacteria in the Ocean by Raman-Based Single-Cell Metabolic Profiling and Genomics
The majority of marine microbes remain uncultured, which hinders the identification and mining of CO2-fixing genes, pathways, and chassis from the oceans. Here, we investigated CO2-fixing microbes in seawater from the euphotic zone of the Yellow Sea of China by detecting and tracking their 13C-bicarbonate (13C-HCO3-) intake via single-cell Raman spectra (SCRS) analysis. The target cells were then isolated by Raman-activated Gravity-driven Encapsulation (RAGE), and their genomes were amplified and sequenced at one-cell resolution. The single-cell metabolism, phenotype and genome are consistent. We identified a not-yet-cultured Pelagibacter spp., which actively assimilates 13C-HCO3-, and also possesses most of the genes encoding enzymes of the Calvin-Benson cycle for CO2 fixation, a complete gene set for a rhodopsin-based light-harvesting system, and the full genes necessary for carotenoid synthesis. The four proteorhodopsin (PR) genes identified in the Pelagibacter spp. were confirmed by heterologous expression in E. coli. These results suggest that hitherto uncultured Pelagibacter spp. uses light-powered metabolism to contribute to global carbon cycling.
De Novo Design of a Highly Stable Ovoid TIM Barrel: Unlocking Pocket Shape towards Functional Design
The ability to finely control the structure of protein folds is an important prerequisite to functional protein design. The TIM barrel fold is an important target for these efforts as it is highly enriched for diverse functions in nature. Although a TIM barrel protein has been designed de novo, the ability to finely alter the curvature of the central beta barrel and the overall architecture of the fold remains elusive, limiting its utility for functional design. Here, we report the de novo design of a TIM barrel with ovoid (twofold) symmetry, drawing inspiration from natural beta and TIM barrels with ovoid curvature. We use an autoregressive backbone sampling strategy to implement our hypothesis for elongated barrel curvature, followed by an iterative enrichment sequence design protocol to obtain sequences which yield a high proportion of successfully folding designs. Designed sequences are highly stable and fold to the designed barrel curvature as determined by a 2.1 Å resolution crystal structure. The designs show robustness to drastic mutations, retaining high melting temperatures even when multiple charged residues are buried in the hydrophobic core or when the hydrophobic core is ablated to alanine. As a scaffold with a greater capacity for hosting diverse hydrogen bonding networks and installation of binding pockets or active sites, the ovoid TIM barrel represents a major step towards the de novo design of functional TIM barrels.
Genetic Circuit Design in Rhizobacteria
Genetically engineered plants hold enormous promise for tackling global food security and agricultural sustainability challenges. However, construction of plant-based genetic circuitry is constrained by a lack of well-characterized genetic parts and circuit design rules. In contrast, advances in bacterial synthetic biology have yielded a wealth of sensors, actuators, and other tools that can be used to build bacterial circuitry. As root-colonizing bacteria (rhizobacteria) exert substantial influence over plant health and growth, genetic circuit design in these microorganisms can be used to indirectly engineer plants and accelerate the design-build-test-learn cycle. Here, we outline genetic parts and best practices for designing rhizobacterial circuits, with an emphasis on sensors, actuators, and chassis species that can be used to monitor/control rhizosphere and plant processes.
Cooperative Virus-Virus Interactions: An Evolutionary Perspective
Despite extensive evidence of virus-virus interactions, not much is known about their biological significance. Importantly, virus-virus interactions could have evolved as a form of cooperation or simply be a by-product of other processes. Here, we review and discuss different types of virus-virus interactions from the point of view of social evolution, which provides a well-established framework for interpreting the fitness costs and benefits of such traits. We also classify interactions according to their mechanisms of action and speculate on their evolutionary implications. As in any other biological system, the evolutionary stability of viral cooperation critically requires cheaters to be excluded from cooperative interactions. We discuss how cheater viruses exploit cooperative traits and how viral populations are able to counteract this maladaptive process.
Meta-Analysis of the Expansion in the Field of Structural Biology of ABC Transporters
ABC transporters are molecular machines which power the solute transport using ATP hydrolysis. The structural biology of ABC transporters has been exploding for the last few years, and this study explores timelines and trends for various attributes such as structural tools, resolution, fold, sources, and group leaders. This study also evidences the significance of mammalian expression systems, advancements in structural biology tools, and the developing interest of group leaders across the world in the remarkably progressing field. The field started in 2002 and bloomed in 2016, and COVID years were really productive to the field. Specifically, the study explores 337 structures of 58 unique ABC transporters deposited in the PDB database from which P-glycoprotein has the largest number of structures. Approximately, 62% of total structures are determined at the resolution of 3-4 Å and 53% of structures belong to fold IV type. With progressive advancements in the field, the field is shifting from prokaryotic to eukaryotic sources and X-ray crystallography to cryoelectron microscopy. In the nutshell, this study uniquely provides the detailed snapshot of the field of structural biology of ABC transporters with real-time data.