Dataset Information

Programmable polyketide biosynthesis platform for production of aromatic compounds in yeast

ABSTRACT: To accelerate the shift to bio-based production and overcome complicated functional implementation of natural and artificial biosynthetic pathways to industry relevant organisms, development of new, versatile, bio-based production platforms are required. Here we present a novel yeast platform for biosynthesis of bacterial aromatic polyketides. The platform is based on a synthetic polyketide synthase system enabling a first demonstration of aromatic polyketide biosynthesis in a eukaryotic host.

ORGANISM(S): Saccharomyces Cerevisiae

SUBMITTER: Chris Petzold

PROVIDER: PXD013388 | panorama | Tue Feb 11 00:00:00 GMT 2020

REPOSITORIES: PanoramaPublic

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Programmable polyketide biosynthesis platform for production of aromatic compounds in yeast.

Jakočiūnas Tadas T Klitgaard Andreas K AK Kontou Eftychia Eva EE Nielsen Julie Bang JB Thomsen Emil E Romero-Suarez David D Blin Kai K Petzold Christopher J CJ Gin Jennifer W JW Tong Yaojun Y Gotfredsen Charlotte Held CH Charusanti Pep P Frandsen Rasmus J N RJN Weber Tilmann T Lee Sang Yup SY Jensen Michael K MK Keasling Jay D JD

Synthetic and systems biotechnology 20200123 1

To accelerate the shift to bio-based production and overcome complicated functional implementation of natural and artificial biosynthetic pathways to industry relevant organisms, development of new, versatile, bio-based production platforms is required. Here we present a novel yeast-based platform for biosynthesis of bacterial aromatic polyketides. The platform is based on a synthetic polyketide synthase system enabling a first demonstration of bacterial aromatic polyketide biosynthesis in a euk ...[more]

PMID: 32021916

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Project description:Obesity-induced insulin resistance of the liver is characterised by increased gluconeogenesis, which contributes to elevated blood glucose levels in individuals with type 2 diabetes. Research into how fatty acids induce insulin resistance has commonly focused on the induction of insulin resistance. We hypothesise that by shifting focus to the reversal of an insulin resistant phenotype, novel insights can be made into the mechanisms by which insulin resistance can be overcome. Using global gene and lipid expression profiling, we aimed to identify biological pathways altered in parallel with restoration of palmitate-induced deregulation of glucose production using metformin and sodium salicylate. FAO hepatoma cells were treated with palmitate (0.075mM, 48h) with or without metformin (0.25mM) and sodium salicylate (2mM) in the final 24h of palmitate treatment, and effects on glucose production were determined. Microarray followed by gene set enrichment analysis was performed to investigate pathway regulation. A lipidomic analysis (HPLC-MS/MS) and measurement of secreted bile acids and cholesterol were performed. Reversal of palmitate-induced impairment of glucose production by metformin and sodium salicylate was characterised by down-regulated expression of metabolic pathways regulating acetyl-CoA to cholesterol and bile acid biosynthesis. Total levels of intracellular and secreted cholesterol and bile acids were not different between impaired and restored glucose production. Total intracellular levels of diacylgycerol, triacylglycerol and cholesterol esters increased with palmitate (impaired glucose production), however, these were not further altered with metformin and sodium salicylate (restored glucose production). Six individual lipid species containing 18:0 and 18:1 side-chains were reduced by metformin and sodium salicylate. Widespread lipid metabolism changes induced by the reversal of palmitate-induced deregulation of glucose production with metformin and sodium salicylate were identified. While cholesterol and bile acid levels remained unchanged, the flux through these pathways may in part explain these findings. The identification of lipid species containing 18:0 and 18:1 side chains being regulated alongside changes to glucose production may indicate potential mediators of glucose production and insulin resistance. Three-condition experiment, Vehicle, Palmitate (PA) and Palmitate (PA) + Metformin (Met) + Sodium Sailcylate (NaS) with biological replicates: 8 Vehicle, 20 PA and 20 PA+Met+NaS , independently grown and harvested. One replicate per array.

Dataset Information

Programmable polyketide biosynthesis platform for production of aromatic compounds in yeast

Publications

Programmable polyketide biosynthesis platform for production of aromatic compounds in yeast.

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