In vivo protein N-acylation
AssigneeDuke University
InventorsMichael David Lynch, Romel Menacho Melgar
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Abstract
Described are a genetically modified microorganism and corresponding methods and products. The genetically modified microorganism may include a first gene that encodes an acyl transferase and a second gene that encodes a peptide or protein. One or both of the first and second gene may be heterologous. The genetically modified microorganism may include a modified acyl-CoA biosynthetic pathway configured for one or more of: inducible biosynthesis of an acyl-CoA and over-accumulation of the acyl-CoA. The genetically modified microorganism may be effective upon fermentation to cause acylation of the peptide or protein by the acyl transferase using the acyl-CoA to provide a N-acylated peptide or protein product.
Claims7
An E. coli microorganism strain, comprising:
- a first gene that encodes a human N-myristol transferase;
- a second gene that encodes a target peptide or protein to be N-acylated operatively linked to an oligonucleotide encoding a substrate for the acyl transferase;
- and
- the E. coli microorganism strain having chromosomal modifications resulting in a genotype comprising ΔfadE::CC-FatBI, yibD-fadD so that, compared to a native acyl-CoA biosynthetic pathway in the native microorganism, the E. coli microorganism strain is configured for inducible expression or overexpression of an endogenous fadD gene and a thioesterase gene upon depletion of phosphate from fermentation medium and
- the genetically modified microorganism being effective upon fermentation to cause acylation of the target peptide or protein by the acyl transferase using the acyl-CoA to provide a N-acylated peptide or protein product.
Dependencies are inferred from the claim text.