Novel methods that may be used for the manufacture of plant alkaloid compounds and novel polynucleotide compounds are provided. The plant alkaloid compounds are useful as medicinal compounds.

Methods for increasing specificity of RNA-guided genome editing, e.g., editing using CRISPR/Cas9 systems.

The present disclosure provides, inter alia, methods for treating a disease characterized by an abnormal level of m6dA in a subject, such as cancer, methods of modifying a nucleic acid from a cell, methods for identifying protein binding sites on DNA, methods of mediating DNA N6-adenine methylation, methods of modulating nucleosome organization and/or transcription in a cell, using MTA1c or any components thereof. The present disclosure also provides methods of generating a synthetic chromosome and synthetic chromosomes made by such methods. Pharmaceutical compositions comprising MTA1c or any components thereof and kits containing such compositions or for carrying out such processes are further provided. Eukaryotic cells, vectors and transgenic organisms comprising MTA1c or any components thereof are also provided. Synthetic chromosomes and methods of making same are also provided.

The present invention relates to genetically modified enzymes obtained by rational design of the active site binding pocket of the prototypic enzyme 4-hydroxyphenylacetate 3-hydroxylase (4HPA3H) for hydroxylating a 4-hydroxyphenyl compound to yield a 3,4-dihydroxyphenyl compound and to biotechnological methods including in vivo and in vitro methods using said enzymes or catalytically active fragments thereof. Further provided is a method either using a suitable oxidase or hydroxylase further enabling the subsequent site specific methylation of the 3,4-dihydroxyphenyl compound in a coupled enzymatic reaction by providing a suitable O-methyltransferase. Finally, compositions obtainable by the aforementioned methods are disclosed.

Methods for increasing specificity of RNA-guided genome editing, e.g., editing using CRISPR/Cas9 systems, using truncated guide RNAs (tru-gRNAs).

Provided herein is a non-naturally occurring microbial organism having a methanol metabolic pathway (MMP) that can enhance the availability of reducing equivalents in the presence of methanol. Such reducing equivalents can be used to increase the product yield of organic compounds produced by the microbial organism, such as 1,4-butanediol (BDO). Also provided herein are methods for using such an organism to produce BDO.

Provided herein are compositions and methods related to the production and detection of a histone H1.0 protein dimethylated at lysine residue 180 (K180) (H1.0K180me2 protein) or a histone H1.0 peptide dimethylated at a lysine residue corresponding to K180 (H1.0K180me2 peptides). The H1.0K180me2 protein and H1.0K180me2 peptides are useful for applications including, but not limited to, molecular diagnostics of DNA damage, genotoxic stress, radiation exposure, and Alzheimer's disease, therapeutics, monitoring of therapeutic regimens, patient stratification, and drug screening. Also provided herein are antibodies specific for the H1.0K180me2 protein and H1.0K180me2 peptides.

Methods and compositions for reducing drug resistance are described. Agents for decreasing m.sup.6A RNA methylation are described. Also described are compositions comprising the agents, methods of making the agents, and methods of using the agents to reduce drug resistance in a subject in need thereof, or to stimulate an immune response.

Methods for increasing specificity of RNA-guided genome editing, e.g., editing using CRISPR/Cas9 systems.

Methods and kits for detecting the presence of at least one target DNA sequence with or without a modification in a DNA molecule are provided.