Chimeric and other variant β-glucuronidase enzymes with enhanced properties as compared to unmodified enzyme are provided. The enzymes of the invention advantageously exhibit enhanced enzymatic activity, enhanced substrate range, enhanced pH range, enhanced temperature range and/or enhanced enzyme stability. Methods of using the variant enzymes for hydrolysis of glucuronide substrates, including opiates and benzodiazepines, are also provided.

Blends of enzymes of the same enzyme class (same EC number), such as beta-glucuronidase enzyme blends, are provided that exhibit synergistic levels of activity across a range of substrates as compared to the activity levels of each enzyme in the blend individually. The blends also may exhibit a greater effective substrate range, as well as greater effective pH and/or temperature ranges as compared to single enzyme preparations. Predictive methods for determining optimal enzyme blends, methods for preparing enzyme blends, enzyme blend compositions, enzyme blend formulations and methods of using such enzyme blends are provided.

Blends of enzymes of the same enzyme class (same EC number), such as beta-glucuronidase enzyme blends, are provided that exhibit synergistic levels of activity across a range of substrates as compared to the activity levels of each enzyme in the blend individually. The blends also may exhibit a greater effective substrate range, as well as greater effective pH and/or temperature ranges as compared to single enzyme preparations. Predictive methods for determining optimal enzyme blends, methods for preparing enzyme blends, enzyme blend compositions, enzyme blend formulations and methods of using such enzyme blends are provided.

This document provides methods and materials for treating osteoarthritis. For example, a mammal having, or at risk for developing, osteoarthritis can be treated by increasing the level of one or more Klotho polypeptides (e.g., one or more alpha-Klotho (α-Klotho) polypeptides) within cells (e.g., chondrocytes) within the mammal.

Provided herein is a protein, referred to as a Pn3Pase protein, that degrades the capsular polysaccharide of serotype 3 Streptococcus pneumoniae. The disclosure includes a genetically modified cell that includes a Pn3Pase protein, and compositions that include the protein, the polynucleotide encoding the protein, the genetically modified cell, or a combination thereof. Also provided are methods for using a Pn3Pase protein, including methods for contacting a S. pneumoniae having a type III capsular polysaccharide with a Pn3Pase protein, increasing deposition of at least one complement component on the surface of a S. pneumoniae, treating an infection in a subject, treating a symptom in a subject, decreasing colonization of a subject by S. pneumoniae, or a combination thereof.

The present disclosure relates to compositions and methods for modulating gene expression and in particular to compositions and methods for increasing expression of Klotho. For example, the present disclosure provides methods for increasing expression of a Klotho gene in a human cell comprising introducing into the cell a CRISPR enzyme and a guide RNA comprising a guide sequence that is substantially complementary to a target sequence within or near the Klotho gene, wherein the guide RNA or the CRISPR enzyme associates with a transcriptional activation domain.

Methods and compositions for reducing reactivation of detoxified drugs, such as xenobiotic agents with narrow therapeutic indices, are provided. The methods include genetically engineering GI microbes in vivo or in vitro to include modifications that decrease or eliminate the presence of enzymes involved in xenobiotic metabolism, such as β-glucuronidase enzymes. Microbes can also be genetically engineered to include a gene for a gut enzyme that provides a protective group to the xenobiotic drug in question.

The invention provides recombinant DNA molecules and constructs, as well as their nucleotide sequences, useful for modulating gene expression in plants. The invention also provides transgenic plants, plant cells, plant parts, and seeds comprising the recombinant DNA molecules operably linked to heterologous transcribable DNA molecules, as are methods of their use.

Provided herein are klotho polypeptide compositions and methods for improving cognitive function in an individual comprising treatment of with klotho polypeptides.

Compositions and methods using shufflon recombinases are presented for use in generating genetic diversity in molecules of interest.