Abstract: Methods and microorganisms for improved malonyl-CoA flux and production of products having malonyl-CoA as a precursor. The methods comprise dynamically regulating, in a stationary phase of a method, a nitrogen regulatory protein. The methods may dynamically regulate more than one gene.

Abstract: The instant specification provides for evolved base editors which overcome deficiencies of those in art (including increased efficiency and/or decreased requirement for specific sequence-context at an editing site) and which are obtained a result of a phage-assisted continuous evolution (PACE) system. In particular, the instant specification provides for evolved cytidine base editors (e.g., based on APOBEC1, CDA, or AID cytidine deaminase domains) which overcome deficiencies of those in art (including increased efficiency and/or decreased requirement for specific sequence-context at an editing site) and which are obtained a result of a phage-assisted continuous evolution (PACE) system.

Abstract: The present disclosure provides a fusion protein useful for treating a non-nuclear organelle associated disorder, such as a genetic disorder, e.g., Friedrich's Ataxia. The fusion protein may comprise a protein of interest to be delivered to a non-nuclear organelle; an organelle targeting sequence (OTS); a cell penetrating peptide (CPP); and a target enhancing sequence (TES); wherein the CPP is capable of interference with delivery of the protein of interest to the non-nuclear organelle; and wherein the TES prevents interference by the CPP. The fusion protein may also comprise a protein of interest to be delivered to a non-nuclear organelle; a CPP and a TES. The present disclosure also provides methods for treating a non-nuclear organelle associated disorder by administering the fusion protein to a subject in need thereof.

Abstract: Disclosed are rationally-designed, non-naturally-occurring meganucleases in which a pair of enzyme subunits having specificity for different recognition sequence half-sites are joined into a single polypeptide to form a functional heterodimer with a non-palindromic recognition sequence. The invention also relates to methods of producing such meganucleases, and methods of producing recombinant nucleic acids and organisms using such meganucleases.

Abstract: The invention provides for systems, methods, and compositions for targeting nucleic acids. In particular, the invention provides non-naturally occurring or engineered DNA-targeting systems comprising a novel DNA-targeting CRISPR effector protein and at least one targeting nucleic acid component like a guide RNA.

Abstract: Disclosed are compositions and methods relating to variant maltohexaose-forming alpha-amylases. The variant alpha-amylases are useful, for example, for starch liquefaction and saccharification, for cleaning starchy stains in laundry, dishwashing, and other applications, for textile processing (e.g., desizing), in animal feed for improving digestibility, and for baking and brewing.

Abstract: Provided herein include methods of making mogroside compounds, e.g., Compound 1, compositions (for example host cells) for making the mogroside compounds, and the mogroside compounds made by the methods disclosed herein, and compositions (for example, cell lysates) and recombinant cells comprising the mogroside compounds (e.g., Compound 1). Also provided herein are novel cucurbitadienol synthases and the use thereof.

Abstract: Compositions and methods for binding to a target sequence of interest are provided. The compositions find use in cleaving or modifying a target sequence of interest, visualization of a target sequence of interest, and modifying the expression of a sequence of interest. Compositions comprise RNA-guided nuclease polypeptides, CRISPR RNAs, trans-activating CRISPR RNAs, guide RNAs, and nucleic acid molecules encoding the same. Vectors and host cells comprising the nucleic acid molecules are also provided. Further provided are CRISPR systems for binding a target sequence of interest, wherein the CRISPR system comprises an RNA-guided nuclease polypeptide and one or more guide RNAs.

Abstract: Proteins, nucleic acids encoding the proteins, compositions comprising the proteins, and methods are provided. The proteins have the ability to be self-targeted to ICAM-1 and, if desired, enzymatically-released at acidic pH. The ICAM-1-targeting peptides are provided as single copies or multiples repeats, and can be separated by linkers from the enzyme segment, from which the ICAM-1 targeting peptides can be released, if desired, at acidic pH. These fusion proteins enhance the activity of the enzyme segment within or liberated from the fusion protein, and provide increased recognition and targeting of diseased organs, transport from the bloodstream across the endothelium into said diseased organ, and intracellular uptake and lysosomal trafficking by cells in them, both in peripheral tissues and the central nervous system. Representative nucleotide and amino acid sequences of these fusion proteins, as well as in vitro, cellular, and in vivo animal data are provided.

Abstract: A microorganism is capable of producing guanidinoacetic acid (GAA) that has been improved by using a carbamate kinase. The microorganism with an improved capacity to provide L-arginine as starting material of the GAA biosynthesis by efficient recycling of ornithine improves the production process of GAA. A method for the fermentative production of GAA and a method for the fermentative production of creatine include the incorporation of the microorganism.

Abstract: The invention relates to selection of bacterial strain for use in treating serotonin deficiency and/or a disease related to serotonin deficiency by culturing bacteria of a lactic acid producing bacterial strain, under aerobic conditions, in a culture medium comprising tryptophan. Any serotonin produced by the bacteria of the lactic acid producing bacterial strain in the culture medium is detected and the lactic acid producing bacterial strain is selected as effective in treating serotonin deficiency and/or a disease related to serotonin deficiency in a subject if serotonin is detected in the culture medium.

Abstract: The present invention provides engineered transaminase polypeptides useful for the synthesis of chiral amine compounds under industrially relevant conditions. The invention also provides polynucleotides encoding the engineered transaminase polypeptides, host cells capable of expressing the engineered transaminases, and methods of using the engineered transaminases for the production of chiral amine compounds.

Abstract: The present invention relates to cleaning compositions comprising polypeptides having peptidoglycan degradation activity, as well as use of the cleaning compositions for cleaning of an item such as a textile or a surface.

Abstract: The present disclosure provides gene edited modified immune cells or precursors thereof (e.g., gene edited modified T cells) comprising an exogenous T cell receptor (TCR) and/or a chimeric antigen receptor (CAR) having specificity for a target antigen, and an insertion and/or deletion in one or more endogenous gene loci, wherein the endogenous gene loci encode regulators of T cell function, thereby resulting in immune cells having enhanced function. Compositions and methods of treatment are also provided. The present invention provides methods of screening for TCR- or CAR-T cells with enhanced immune function (e.g., T cell efficacy, T cell memory, and/or T cell persistence).

Abstract: Provided herein are methods and compositions comprising a bacterium or a metabolite thereof for enhancing mitochondrial and/or peroxisomal function.

Abstract: The present invention discloses a recombinant fused polypeptide, a preparation method therefor, and use thereof. The recombinant fused polypeptide is represented by the following general formula: X-linker1-Y; Y-linker1-X; X-linker2-Y; Y-linker2-X, where X is PRCWRGEGGGGIVRRADRAAVPGGGGRGD; and Y is Acetyl-SDKPGGGGTSLDASIIWAMMQNGGGGLSKL. The recombinant fused polypeptide according to the present invention can treat various fibrosis diseases and symptoms, and therapeutic use includes anti-pulmonary fibrosis, anti-hepatic fibrosis, anti-skin fibrosis, anti-renal fibrosis, anti-myocardial fibrosis, and resistance to lung tissue lesions.

Abstract: A tandem DNA element capable of enhancing protein synthesis efficiency, in particular, the nucleic acid construct is formed by an IRES enhancer (such as ScBOI1, ScFLO8, ScNCE102, ScMSN1, KlFLO8, KlNCE102, KlMSN1, KlBOI1) derived from eukaryotic cells (such as yeast), a ? sequence, and a yeast-specific Kozak sequence in tandem. The use of the nucleic acid construct in a yeast-based in vitro biosynthesis system (such as a yeast-based in vitro protein synthesis system) can significantly improve protein synthesis efficiency.

Abstract: Disclosed is a method for producing, in one step, “made to measure” double-stranded DNA vectors from molecular bricks including sequences of interest in the presence of a one and only type IIs restriction enzyme.

Abstract: Engineered nucleic acids encoding genome editing system components are provided, as are engineered RNA-guided nucleases that include inserts encoded in part by cellular genomic or other sequences recognized by guide RNAs.

Abstract: The invention provides for systems, methods, and compositions for altering expression of target gene sequences and related gene products. Provided are structural information on the Cas protein of the CRISPR-Cas system, use of this information in generating modified components of the CRISPR complex, vectors and vector systems which encode one or more components or modified components of a CRISPR complex, as well as methods for the design and use of such vectors and components. Also provided are methods of directing CRISPR complex formation in eukaryotic cells and methods for utilizing the CRISPR-Cas system. In particular the present invention comprehends optimized functional CRISPR-Cas enzyme systems.