Biology subjects

Whitehead, P.

Publications and source records attributed to Whitehead, P..

3 recordsLinked to original sources

bioRxiv2026

Complete biosynthesis of penicillin G in Nicotiana benthamiana

Commercial penicillin production has relied on microbial fermentation for more than 80 years. Here, we engineered the plant, Nicotiana benthamiana, to produce penicillin G in its leaves by transient expression of up to seven fungal biosynthetic genes. Remarkably, all recombinant proteins localize to the analogous subcellular compartments without engineering signal peptide sequences or post-translational modification sites. Although non-ribosomal peptide synthetases occur widely in fungi and bacteria to produce a plethora of specialized metabolites, their evolutionary distribution does not extend to plants. Our results now open a new metabolic frontier for natural product synthesis, and offer possibilities to address global health concerns through an alternative biotechnology platform for fungal-derived pharmaceutical production.

synthetic biology↗

bioRxiv2022

Ancestry-related differences in chromatin accessibility and gene expression of APOE4 are associated with Alzheimer disease risk

BackgroundEuropean local ancestry (ELA) surrounding APOE4 is associated with a higher risk for Alzheimer Disease (AD) compared to African local ancestry (ALA). We previously demonstrated significantly higher APOE4 expression in ELA vs ALA in the frontal cortex of APOE4/4 AD patients. Differences in chromatin accessibility could contribute to these differences in APOE4 expression. MethodsWe performed single nuclei Assays for Transposase Accessible Chromatin sequencing (snATAC-seq) and single nuclei RNA sequencing (snRNA-seq) from frozen frontal cortex of six ALA and six ELA AD patients, all homozygous for local ancestry and APOE4. ResultsWe demonstrated that APOE4, including its promoter area, has greater chromatin accessibility in ELA vs ALA astrocytes. This increased accessibility in ELA astrocytes extended genome wide. Genes with increased accessibility and expression in ELA in astrocytes were enriched for synaptic function, cholesterol processing and astrocyte reactivity. ConclusionOur results suggest that increased chromatin accessibility of APOE4 in astrocyte with the ELA contributes to the observed elevated APOE4 expression, corresponding to the increased AD risk in ELA vs ALA APOE4/4 carriers.

neuroscience↗

bioRxiv2020

Increased APOEϵ4 expression is associated with reactive A1 astrocytes and the difference in Alzheimer Disease risk from diverse ancestral backgrounds

APOE{varepsilon}4 African local genomic ancestry (LA) confers less risk for Alzheimer disease (AD) relative to European LA (LA) carriers. Single nucleus RNA sequencing from AD-APOE{varepsilon}4/4 frontal cortex found European LA carriers have a 1.45-fold greater APOE{varepsilon}4 expression (p< 1.8 E10-313) and are associated with a unique A1 reactive astrocyte cluster. This suggests a potential mechanism for the increased risk for AD seen in European LA carriers of APOE{varepsilon}4.

genomics↗