The present invention relates to an alternative co-substrate of ketoglutaric acid-dependent dioxygenases for functional production and control of same, with the aim of achieving therapeutic effects against cancer, neurodegenerative diseases and age related diseases. Epigenetically induced diseases caused by dysregulation and in particular also by metabolic dysfunction in the citric acid cycle are likewise targeted by this therapy.

A protein antigen combination for detecting Alzheimer's disease autoantibodies in human serum sample and an application thereof are disclosed. The protein antigen combination includes at least two protein fragments selected from the following proteins: MAPT, ADARB1, P21, DNAJC8, RAGE, ASXL1, and JMJD2D. Based on the protein antigen composition, a kit for diagnosis, especially for early diagnosis of Alzheimer's disease or its related risks, can be prepared. By using the protein antigen composition provided by the invention, early Alzheimer's disease can be quickly and accurately diagnosed, which has important practical significance.

Provided herein are recombinant adeno-associated virus (rAAV) compositions that can restore phenylalanine hydroxylase (PAH) gene function in cells, and methods for using the same to treat diseases associated with reduction of PAH gene function (e.g., PKU). Also provided are nucleic acids, vectors, packaging systems, and methods for making the adeno-associated virus compositions.

A microbial oil is obtained from Labyrinthulomycetes in which a gene for fatty acid biosynthesis has been disrupted or an expression of the gene has been inhibited to highly accumulate the fatty acid. The microbial oil typically contains: (a) 1.5% or more of arachidonic acid (AA) based on a total amount of fatty acid; (b) 0.2% or more of dihomo-γ-linolenic acid (DGLA) based on the total amount of fatty acid; (c) 0.04% or more of eicosatetraenoic acid (ETA) based on the total amount of fatty acid; (d) 3.8% or more of eicosapentaenoic acid (EPA) based on the total amount of fatty acid; (e) 13.7% or less of n-6 docosapentaenoic acid (n-6DPA) based on the total amount of fatty acid; and (f) 43.9% or less of docosahexaenoic acid (DHA) based on the total amount of fatty acid.

The present invention relates a variant polypeptide having kaurenoic acid 13-hydroxylase activity, which variant polypeptide comprises an amino acid sequence which, when aligned with a kaurenoic acid 13-hydroxylase comprising the sequence set out in SEQ ID NO: 1, comprises at least one substitution of an amino acid residue corresponding to any of amino acids 72, 85, 108, 127, 129, 141, 172, 195, 196, 197, 199, 226, 236, 291, 302, 361 or 464, said positions being defined with reference to SEQ ID NO: 1 and wherein the variant has one or more modified properties as compared with a reference polypeptide having kaurenoic acid 13-hydroxylase activity. A variant polypeptide of the invention may be used in a recombinant host for the production of steviol or a steviol glycoside.

A method for identifying any of the presence, location and phasing of modified cytosines (C) in long stretches of nucleic acids is provided. In some embodiments, the method may comprise (a) reacting a first portion of a nucleic acid sample containing at least one C and/or at least one modified C with a DNA glucosyltransferase and a cytidine deaminase to produce a first product and/or reacting a second portion of the sample with a dioxygenase, optionally a DNA glucosyltransferase and a cytidine deaminase to produce a second product and; (b) comparing the sequences from the first and optionally the second product obtained in (a), or amplification products thereof, with each other and/or an untreated reference sequence to determine which Cs in the initial nucleic acid fragment are modified. A modified TET methylcytosine dioxygenase with improved efficiency compared to unmodified TET2 at converting methylcytosine to carboxymethylcytosine is also provided.

The present disclosure relates to the biosynthesis of indigoid dye precursors and their conversion to indigoid dyes. Specifically, the present disclosure relates to methods of using polypeptides to produce indigoid dye precursors from indole feed compounds, and the use of the indigoid dye precursors to produce indigoid dyes.

A recombinant microbial host cell having improved in vivo conversion of reticuline and derivatives thereof (such as thebaine and/or oripavine) to relevant downstream opioids (such as neopinone, oripavine, northebaine, nororipavine or morphinone) and related compounds (such as heroin, morphine, codeine, thebaine, oripavine, oxycodone, hydrocodone, hydromorphone, oxymorphone, buprenorphine, naltrexone, naloxone or nalbuphine), wherein the microbial (such as fungal) host cell is heterologously expressing at least one functional transporter protein capable of transporting reticuline or a derivative thereof (such as thebaine and/or oripavine) and a heterologously expressed enzyme capable of acting upon reticuline or a derivative thereof. The invention also relates to uses of the microbial host cells and methods of making an opioid compound and/or opioid precursor compound and/or opioid derivative of interest.

The present disclosure relates to a tyrosine hydroxylase (TH) variant lacking 60 to 120 amino acid residues at the N terminus, and a pharmaceutical composition comprising the TH variant lacking 60 to 120 amino acid residues at the N terminus and the aromatic L-amino acid decarboxylase (AADC). The present disclosure further relates to a nucleotide construct, a vector plasmid, a cell or a virus comprising the TH variant or the pharmaceutical composition, as well as use of the virus in the manufacture of a medicament for treating neurodegenerative diseases (e.g., Parkinson's Disease).

The subject invention provides novel plants that are not only resistant to 2,4-D, but also to pyridyloxyacetate herbicides. Heretofore, there was no expectation or suggestion that a plant with both of these advantageous properties could be produced by the introduction of a single gene. The subject invention also includes plants that produce one or more enzymes of the subject invention “stacked” together with one or more other herbicide resistance genes. The subject invention enables novel combinations of herbicides to be used in new ways. Furthermore, the subject invention provides novel methods of preventing the development of, and controlling, strains of weeds that are resistant to one or more herbicides such as glyphosate. The preferred enzyme and gene for use according to the subject invention are referred to herein as AAD-12 (AryloxyAlkanoate Dioxygenase). This highly novel discovery is the basis of significant herbicide tolerant crop trait and selectable marker opportunities.