5-hydroxytryptophan (5-HTP), a precursor of serotonin, is produced in a microbial host cell. A modified bacterial phenylalanine 4-hydroxylase (P4H) catalyzes the tryptophan 5-hydroxylation reaction. Optionally the host cell includes a cofactor regeneration mechanism, allowing continuous production of 5-HTP without supplementation of exogenous cofactors.

Aspects of the present disclosure are drawn to methods of improving the expression of secreted cuproenzymes from host cells by manipulating the expression level of one or more proteins involved in copper transport in the host cell, e.g., membrane-bound copper transporting ATPases and soluble copper transporters. The present disclosure also provides compositions containing such improved host cells as well as products derived from the improved host cells that contain one or more cuproenzymes of interest.

The present disclosure provides recombinant bacterial cells that have been engineered with genetic circuitry which allow the recombinant bacterial cells to sense a patient's internal environment and respond by turning an engineered metabolic pathway on or off. When turned on, the recombinant bacterial cells complete all of the steps in a metabolic pathway to achieve a therapeutic effect in a host subject. These recombinant bacterial cells are designed to drive therapeutic effects throughout the body of a host from a point of origin of the microbiome. Specifically, the present disclosure provides recombinant bacterial cells comprising a heterologous gene encoding a branched chain amino acid catabolism enzyme. The disclosure further provides pharmaceutical compositions comprising the recombinant bacteria, and methods for treating disorders involving the catabolism of branched chain amino acids using the pharmaceutical compositions disclosed herein.

The present disclosure provides systems and methods for increasing production of an alkaloid product through the epimerization of a (S)-1-benzylisoquinoline alkaloid to a (R)-1-benyzlisoquinoline alkaloid via an engineered epimerase in an engineered host cell. A (S)-1-benzylisoquinoline alkaloid is contacted with said engineered epimerase. Contacting said (S)-1-benzylisoquinoline alkaloid with said engineered epimerase converts said (S)-1-benzylisoquinoline alkaloid to said (R)-1-benzylisoquinoline alkaloid.

Described are nicotine-degrading enzyme variants that exhibit increased nicotine-degrading activity and/or decreased immunogenicity relative to the wild-type NicA2 enzyme, compositions comprising the variants, and methods using them.

Disclosed herein are compositions and methods for reducing the antigenicity of molecules, wherein the molecule comprises a uricase. The antigenicity of a molecule may be reduced or eliminated by conjugating at least one branched polymer to the molecule to form a molecule-polymer conjugate. The branched polymer may include a backbone and a plurality of side chains, each side chain covalently attached to the backbone.

Disclosed is a method for diagnosing a mood disorder or susceptibility to a mood disorder, including depressive disorders and bipolar disorder, from a biological sample taken from a subject. The method includes detecting markers of monoamine oxidase-A (MAO-A) in the biological sample; determining MAO-A concentration from the markers; and correlating the MAO-A concentration in the biological sample to a control group which does not have a mood disorder in order to diagnose or determine susceptibility to the mood disorder in the subject. Also disclosed is a method of detecting peripheral markers of MAO-A for the diagnosis of a mood disorder or susceptibility to a mood disorder. Also provided are polypeptide markers.

The invention relates to a whole-cell catalyst which expresses a recombinant α-dioxygenase or the combination of a recombinant fatty acid reductase and a phosphopantetheinyl transferase which phosphopantetheinylates the fatty acid reductase, and which expresses, in addition to the α-dioxygenase and/or the combination of fatty acid reductase and phosphopantetheinyl transferase, a transaminase, wherein the phosphopantetheinyl transferase and/or transaminase is preferably recombinant; and also to a process for converting a carboxylic acid or dicarboxylic acid or a monoester thereof to an amine or diamine, comprising the steps of contacting the carboxylic acid or dicarboxylic acid or the monoester thereof with a phosphopantetheinylated fatty acid reductase or an α-dioxygenase and contacting the product with a transaminase.

The present disclosure provides compositions and methods for rapid production of chemicals in genetically engineered microorganisms in a large scale. Also provided herein is a high-throughput metabolic engineering platform enabling the rapid optimization of microbial production strains. The platform, which bridges a gap between current in vivo and in vitro bio-production approaches, relies on dynamic minimization of the active metabolic network.

The invention provides a whole cell catalyst which expresses a recombinant α-dioxygenase or the combination of a recombinant fatty acid reductase and a phosphopantetheinyl transferase phosphopantetheinylating the fatty acid reductase, and which in addition to the α-dioxygenase and/or the combination of fatty acid reductase and phosphopantetheinyl transferase expresses a transaminase, characterized in that the phosphopantetheinyl transferase and/or transaminase is preferably recombinant; and a method for the conversion of a fatty acid, ω-hydroxy fatty acid, ω-oxo fatty acid or a monoester thereof to an amine, comprising oxidation of the fatty acid, ω-hydroxy fatty acid, ω-oxo fatty acid or the monoester thereof to an oxidation product by contacting with an alkane hydroxylase and/or alcohol dehydrogenase, contacting the oxidation product with a phosphopantetheinylated fatty acid reductase or a α-dioxygenase to give an aldehyde, and contacting the aldehyde with a transaminase.