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Hyperthermophilic Single-Peptide For Deconstruction Of Crystalline Cellulose

Cellulose, the major component of plant biomass, is considered the most abundant biopolymer. Certain microorganisms are able to convert the monomer of cellulose, glucose, into various products useful in the production of biofuels and other methods. Cellulose is highly stable, has a high storage potential, low cost, and plentiful supply. Based on these and other properties, cellulose and enzymes capable of degrading and hydrolyzing it are useful in the sequestration, storage, and production of bioenergy.  Crystalline cellulose is composed of linear polymers of β1-4 linked glucose, held in a tightly crosslinked crystalline lattice by a high degree of intermolecular hydrogen bonding. This structure confers stability but also hinders efficient deconstruction of cellulose. Strategies for commercial depolymerization of cellulose typically combine pretreatment to disrupt the crystalline structure, followed by enzymatic hydrolysis. Disruption of the crystalline structure and chemical hydrolysis typically requires high temperatures and low pH. Enzymatic hydrolysis generally occurs under milder conditions. The degree of pretreatment required and the expense of subsequent cleanup steps are affected by properties of the enzymes used. Bacteria capable of degrading cellulose include those belonging to the genera Aquifex, Rhodothermus, Thermobifida, Anaerocellum, and Caldicellulosiruptor. A recombinant thermostable endoglucanase of Aquifex aeolicus produced in E. coli showed maximal activity at 80° C. and pH 7.0 with a half-life of 2 h at 100° C.  UC Berkeley investigators have engineered a polypeptide having cellulase activity for hydrolysis and degradation of cellulose-containing biomass.

High-Throughput Selection Platform to Obtain NMN+-Utilizing Enzymes Through Directed Evolution

Noncanonical redox cofactor-based biotransformation is an attractive low-cost alternative to traditional cell-free reductive biotransformation. However, engineering enzymes to utilize noncanonical redox cofactors has been challenging. Addressing this problem, researchers at UC Irvine have developed a high-throughput directed evolution platform that enables development of such enzymes with ~147-fold improved catalytic efficiency, which translates to an industry-viable total turnover number of ~45,000 in cell-free biotransformation without requiring high cofactor concentrations.

Biomimetic Chemical Compounds for Capturing Carbon Dioxide from Power Plant Stacks and the Atmosphere

Researchers at the University of California, Davis have developed synthetic biochemical compounds that capture carbon dioxide from the atmosphere or sources such as power plants. These new derivatives mimic how some plants capture carbon dioxide from the air and use it for photosynthesis.

Precision Graphene Nanoribbon Wires for Molecular Electronics Sensing and Switch

The inventors have developed a highly scalable multiplexed approach to increase the density of graphene nanoribbon- (GNR) based transistors. The technology forms a single device/chip (scale to 16,000 to >1,000,000 parallel transistors) on a single integrated circuit for single molecule biomolecular sensing, electrical switching, magnetic switching, and logic operations. This work relates to the synthesis and the manufacture of molecular electronic devices, more particularly sensors, switches, and complimentary metal-oxide semiconductor (CMOS) chip-based integrated circuits.Bottom-up synthesized graphene nanoribbons (GNRs) have emerged as one of the most promising materials for post-silicon integrated circuit architectures and have already demonstrated the ability to overcome many of the challenges encountered by devices based on carbon nanotubes or photolithographically patterned graphene. The new field of synthetic electronics borne out of GNRs electronic devices could enable the next generation of electronic circuits and sensors.  

(SD2020-014) Biosynthetic Production Of L-4-Chlorokynurenine

The non‐proteinogenic amino acid l‐4‐chlorokynurenine (l‐4‐Cl‐Kyn) is a next‐generation, fast‐acting oral prodrug for the treatment of major depressive disorder. Additional studies report that this drug candidate is effective in animal models for the treatment of neuropathic pain, epilepsy, and Huntington's disease.  After active transport across the blood–brain barrier, it is enzymatically converted into the active agent 7‐chlorokynurenic acid, which is a highly selective competitive antagonist of the N‐methyl‐d‐aspartic acid (NMDA) receptor.   Suicide is 2-7x higher in Veterans than non-veterans, and may be related to brain kynurenine pathway (KP) dysregulation and NMDA receptor (NMDAR) hyperactivation.  L-4-Chlorokynurenine (L-4-Cl-Kyn) is a neuropharmaceutical drug candidate that is in development for the treatment of major depressive disorder (Double-Blind, Placebo-Controlled, Phase 2 Trial to Test Efficacy and Safety of AV-101 (L-4-chlorokynurenine) as Adjunct to Current Antidepressant Therapy in Patients With Major Depressive Disorder (the ELEVATE Study)).

In plantae production of heterologous proteins using viral amplicons

Researchers at the University of California, Davis have developed a viral amplicon-based vector system for heterologous protein expression and production in plants.

Spray Dry Method for Calcium Cross-linked Alginate Encapsulation of Biological and Chemical Moieties via the Use of Chelating Agents

Researchers at the University of California, Davis have developed a one-step spray dry calcium cross-linked alginate encapsulation process where the calcium is released from a chelating agent.

Method For Production Of Fatty Acids In Blue-Green Algae

Currently, renewable fatty acids are obtained solely from plant oils. Medium chain fatty acids (C8-C14) are typically sourced from coconut and palm oil, whereas longer chain saturated and unsaturated fatty acids are typically sourced from tallow, soy, corn or sunflower oil. Fatty acids are widely used for food, personal care products, industrial applications (e.g., lubricants, adhesives, detergents and plastics), as well as increasingly as biofuels. The demand for renewable fatty acids is rising and expanding. Given the current understanding of biological pathways it becomes possible to utilize other organisms, especially microorganisms, for the production of renewable chemicals such as fatty acids.

Cephalopod-Inspired Adaptive Infrared Camouflage Materials and Systems

This technology is a new class of materials capable of thermal regulation and active camouflage. These cephalopod-inspired materials, configurable to different geometries, can be used in many sectors, ranging from consumer to industrial to military applications.

(SD2018-178) Engineering Polyketide Synthase Machinery in Synechococcus Cyanobacteria

Complex polyketides include a family of natural products that possess a wide variety of pharmacological or biological activities. Numerous polyketides and their semisynthetic derivatives have been approved for clinical use in humans or animals, including antibiotics, antifungal agents, immunosuppressants, antiparasitic agents and insecticides. All these natural products share a common mechanism of biosynthesis and are produced by a class of enzymes called polyketide synthases (PKSs). Besides their essential role in the biosynthesis of a vast diversity of natural products, the versatility of PKSs can be further emphasized as they can be redesigned and repurposed to produce novel molecules that could be used as fuels, industrial chemicals, and monomers. Most polyketide producers are slow-growing, recalcitrant to genetic manipulation, or even non-culturable.Cyanobacteria are particularly attractive for the production of natural compounds because they have minimal nutritional demands and several strains have well established genetic tools. 

Synthetic Algal Promoters as a Tool for Increasing Nuclear Gene Expression in Green Algae

Algae have enormous potential as bio-factories for the efficient production of a wide array of high-value products, and eventually as a source of renewable biofuels. However, tools for engineering the nuclear genomes of algae remain scarce and limited in functionality, in part due to lack of strong promoters.

A Highly Error-Prone Orthogonal Replication System For Targeted Continuous Evolution In Vivo

Inventors at UC Irvine have engineered an orthogonal DNA replication system capable of rapid, accelerated continuous evolution. This system enables the directed evolution of specific biomolecules towards user-defined functions and is applicable to problems of protein, enzyme, and metabolic pathway engineering.

Non-Oxidative Glycolysis For Production Of Acetyl-CoA Derived Compounds

The Liao group at UCLA has constructed a Non-Oxidative Glycolysis pathway for the synthesis of biofuel precursors with a 100% carbon conversion rate.

Biomass-Derived Polymers And Copolymers Incorporating Monolignols And Their Derivatives

UCLA researchers in the Departments of Bioengineering, Chemistry and Biochemistry have developed a novel synthetic strategy for the fabrication of biomass-derived polymers incorporating underutilized lignin derivatives.

A Molecular Rheostat Design that Maintains ATP Levels Needed to Drive Cell-Free Synthetic Biochemistry Systems

UCLA researchers in the Department of Chemistry and Biochemistry have developed a system for regulation of cofactors in cell free biochemical production.

Rapid, Portable And Cost-Effective Yeast Cell Viability And Concentration Analysis Using Lensfree On-Chip Microscopy And Machine Learning

UCLA researchers in the Department of Electrical Engineering have developed a new portable device to rapidly measure yeast cell viability and concentration using a lab-on-chip design.

Renewable Energy Synthesis System

Researchers at the University of California, Davis have developed a novel system for acetoin and 2,3-butanediol synthesis from carbon dioxide.

Method and System for Ultra High Dynamic Range Nucleic Acid Quantification

Researchers at UC Irvine developed a device and method that combines the high dynamic range and high accuracy of digital PCR (dPCR) with the real-time analysis of quantitative PCR (qPCR) to achieve a ultra-high dynamic range PCR over 10 to 12 orders of magnitude. The present method is accomplished by a highly integrated design that optimally packs, thermocycles, and images as many as 1 million reaction vessels.

Self-Adaptive Control And Optimization Of Ultrafiltration

UCLA researchers in the Department of Chemical and Biomolecular engineering have developed a novel UF-RO system.

Mammalian Cell Culture Optimization

Biotherapeutic proteins manufactured in cell culture systems have transformed modern medicine. Selling many tens of billions per year, new biotherapeutics such as monoclonal antibodies have delivered dramatic clinical results, while posing significant manufacturing problems.: During the cell culture manufacturing process, toxic bioproducts such as lactate and ammonia have posed considerable challenges in bioprocessing, since they limit cell growth and impact critical quality attributes of recombinant protein production (e.g., therapeutic drugs, enzymes). That is because the lactate alters the regulation of biosynthetic enzymes, and can lead to changes in pH in the culture. To mitigate the negative effects of lactic acid accumulation and control the culture pH, chemical ‘base’ is added to the media during the course of a bioprocess. However, the base addition negatively impacts the bioprocess by inhibiting growth and shortening the length of time in which the cells can produce the recombinant protein. This leads to reduced yield, and increased cost-of-goods. Thus, it is of great interest to eliminate lactate production, and UC San Diego researchers have recently developed a new process for achieving this.  

Controllable Emulsification and Point-Of-Care Assays Driven by Magnetic Induced Movement of the Fluid

UCLA researchers in the Department of Bioengineering have developed a microfluidic droplet generation technique that only uses magnetic forces to emulsify ferrofluid containing solutions.

A Low-Profile Flow Shear Sensing Unit

UCLA researchers have developed an accurate low-profile shear sensing unit that is viable for both gas and liquid flows.

Novel Synthesis of 2,5- Dimethylfuran from 5- (Chloromethyl)furfural

Researchers at the University of California, Davis have developed an efficient synthesis of 2,5- dimethylfuran (DMF) from 5- (chloromethyl)furfural (CMF).

Salmonella-Based Gene Delivery Vectors and their Preparation

Nucleic acid-based gene interference technologies, including ribozymes and small interfering RNAs (siRNAs), represent promising gene-targeting strategies for specific inhibition of mRNA sequences of choice. A fundamental challenge to use nucleic acid-based gene interfering approaches for gene therapy is to deliver the gene interfering agents to appropriate cells in a way that is tissue/cell specific, efficient and safe. Many of the currently used vectors are based on attenuated or modified viruses, or synthetic vectors in which complexes of DNA, proteins, and/or lipids are formed in particles, and tissue-specific vectors have been only partially obtained by using carriers that specifically target certain cell types. As such, efficient and targeted delivery of M1GS sequences to specific cell types and tissues in vivo is central to developing this technology for gene targeting applications. Invasive bacteria, such as Salmonella, possess the ability to enter and transfer genetic material to human cells, leading to the efficient expression of transferred genes. Attenuated Salmonella strains have earlier been shown to function as a carrier system for delivery of nucleic acid-based vaccines and anti-tumor transgenes. Salmonella-based vectors are low cost and easy to prepare. Furthermore, they can be administrated orally in vivo, a non-invasive delivery route with significant advantage. Thus, Salmonella may represent a promising gene delivery agent for gene therapy. Scientists at UC Berkeley have developed a novel attenuated strain of Salmonella, SL101, which exhibited high gene transfer activity and low cytotoxicity/pathogenicity while efficiently delivering ribozymes, for expression in animals. Using MCMV infection of mice as the model, they demonstrated that oral inoculation of SL101 in animals efficiently delivered RNase P-based ribozyme sequence into specific organs, leading to substantial expression of ribozyme and effective inhibition of viral infection and pathogenesis. This strategy could easily be adopted deliver other gene targeting technologies.

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