Provided herein are methods and compositions for highly precise base editing and single strand nicking. In particular, provided herein are methods for producing a genetically modified cell where the methods employ a universal, highly precise base editor or staggered Cas9 editor for precise base editing with minimal off-target or bystander effects.

Fumonisins are a type of mycotoxin that contaminate different products, for example, feed and food products, including corn-based products, which can lead to serious health risks to humans and livestock. Current methods for detoxifying fumonisin-contaminated products are complex and expensive. The present disclosure provides a recombinant microbial host cell expressing an heterologous polypeptide having fumonisin amine oxidase activity, the recombinant microbial host cell comprising an heterologous nucleic acid molecule encoding the heterologous polypeptide having fumonisin amine oxidase activity, a variant thereof or a fragment thereof. The heterologous polypeptide having fumonisin amine oxidase activity can be used to detoxify a fumonisin mycotoxin present in feed and food products, for example from grains and products derived from grains.

Provided herein are methods and compositions for producing phenylpropanoid derivatives, such as chalcones and stilbenes, and dihydrophenylpropanoid derivatives, such as dihydrochalcones and dihydrostilbenes, in microorganisms. In particular, the disclosure provides recombinant microorganisms and methods of use thereof for producing phenylpropanoid derivative compounds and dihydrophenylpropanoid derivative compounds.

Provided herein are genetically engineered cells containing one or more modulated metabolic genes, where the expression of the modulated metabolic gene(s) can be greater than that of an unmodified control. Also provided herein are methods of making the genetically engineered cells using synergistic activation mediator CRISPR-Cas9. Further provided herein are high throughput assays that can employ the genetically engineered cells provided herein.

Provided herein are genetically engineered cells containing one or more modulated metabolic genes, where the expression of the modulated metabolic gene(s) can be greater than that of an unmodified control. Also provided herein are methods of making the genetically engineered cells using synergistic activation mediator CRISPR-Cas9. Further provided herein are high throughput assays that can employ the genetically engineered cells provided herein.

The present invention relates to transcription regulatory elements (TREs) based on the combination of a hAAT sequence element and an AMBP sequence element and which promote greater expression than HCR-hAAT. The invention further relates to compositions comprising the AAV vectors, as well as methods of gene therapy based on the use of such vectors and compositions.

Provided herein are methods and compositions for producing phenylpropanoid derivatives, such as chalcones and stilbenes, and dihydrophenylpropanoid derivatives, such as dihydrochalcones and dihydrostilbenes, in microorganisms. In particular, the disclosure provides recombinant microorganisms and methods of use thereof for producing phenylpropanoid derivative compounds and dihydrophenylpropanoid derivative compounds.