Engineering Yarrowia lipolytica as a chassis for de novo synthesis of aromatic-derived natural products and chemicals

BioRxiv : the Preprint Server for Biology
Y. GuPeng Xu


Yarrowia lipolytica is an attractive host to upgrade renewable low-cost carbon feedstocks to high-value commodity chemicals and natural products. In this work, we systematically characterized and removed the rate-limiting steps of the shikimate pathway and achieved de novo synthesis of five aromatic chemicals in Y. lipolytica. We determined that engineering feedback-insensitive DAHP synthases and eliminating amino acids formation are critical steps to mitigate the feedback regulation of shikimate pathway. Further overexpression of heterologous phosphoketolase and deletion of pyruvate kinase provided a sustained metabolic driving force that channels E4P (erythrose 4-phosphate) and PEP (phosphoenolpyruvate) precursors through the shikimate pathway. Precursor competing pathways and byproduct formation pathways were also blocked by inactivating chromosomal genes. To demonstrate the utility of our engineered chassis strain, three natural products, 2-PE, p-coumaric acid and violacein, which were derived from phenylalanine, tyrosine and tryptophan, respectively, were chosen to test the chassis performance. We obtained 2426.22 mg/L of 2-phenylethanol (2-PE), 593.53 mg/L of p-coumaric acid, 366.30 mg/L of violacein and 55.12 mg/L of deo...Continue Reading

Related Concepts

DNA Methylation [PE]
Entire Scalp
Specimen Type - Fibroblasts
Pluripotent Stem Cells
Somatic Mutation
Spatial Distribution
Cell Culture Techniques

Related Feeds

BioRxiv & MedRxiv Preprints

BioRxiv and MedRxiv are the preprint servers for biology and health sciences respectively, operated by Cold Spring Harbor Laboratory. Here are the latest preprint articles (which are not peer-reviewed) from BioRxiv and MedRxiv.