The invention provides genetically engineered microorganisms and methods for producing chorismate-derived products, such as para-hydroxybenzoic acid, salicylate, 2-aminobenzoate, 2,3-dihydroxybenzoate, and 4-hydroxycyclohexane carboxylic acid. Typically, the microorganism comprises at least one of (a) an exogenous chorismate pyruvate lyase, (b) an exogenous isochorismate synthase, (c) an exogenous isochorismate pyruvate lyase, and (d) a prephenate synthase comprising a disruptive mutation.

A transformant constructed by introducing a gene which encodes an enzyme having chorismate-pyruvate lyase activity into a coryneform bacterium as a host is capable of efficiently producing 4-hydroxybenzoic acid or a salt thereof from a sugar. When the transformant is cultured under aerobic conditions where the transformant does not grow, 4-hydroxybenzoic acid or a salt thereof can be produced in a particularly efficient manner.

The mutant chorismate-pyruvate lyase (A) or (B) as described below is capable of producing 4-hydroxybenzoic acid or a salt thereof with sufficient practical efficiency.

(A) A mutant chorismate-pyruvate lyase obtained by replacing the valine at position 80 in a chorismate-pyruvate lyase (ubiC) from Pantoea ananatis consisting of the amino acid sequence of SEQ ID NO: 1 with one or more other amino acids.

(B) A mutant chorismate-pyruvate lyase obtained by replacing an amino acid in another chorismate-pyruvate lyase, the amino acid being at a position enzymologically homologous with that of the above valine, with one or more other amino acids.

Aspects of the disclosure relate to methods and compositions for diagnosing and/or treating subjects having one or more symptoms of Autism Spectrum Disorder (ASD) or subjects at risk of developing ASD. In some embodiments, methods comprise determining and/or modulating levels of chorismate and/or a molecule within a chorismate metabolic pathway in a subject. In some embodiments, methods comprise determining and/or modulating levels of a microbial feature (e.g., a Sarcina bacterium) in a subject. In some embodiments, methods comprise determining and/or modulating levels of proton flux in a gastrointestinal tract in a subject.

A method for conferring tolerance to a 4-hydroxyphenylpyruvate dioxygenase (HPPD) inhibitor herbicide in a plant by expressing one or more polypeptide components of an exogenous plastoquinone-9 pathway in the plant. Nucleic acids, vectors, transgenic cells and transgenic plants useful in such a method are also disclosed.