In vivo protein n-acylation

A genetically modified microorganism, comprising:

• a first gene that encodes an acyl transferase;
• a second gene that encodes a peptide or protein, one or both of the first and second gene being heterologous with respect to a corresponding native microorganism;
• and
• a modified acyl-CoA biosynthetic pathway that is, compared to a native acyl-CoA biosynthetic pathway in the native microorganism, configured for one or more of:
• inducible biosynthesis of an acyl-CoA and over-accumulation of the acyl-CoA,
• wherein either the acyl transferase is characterized by a mutation in an acyl-CoA binding site or the second gene is operatively linked to an oligonucleotide encoding a substrate for the acyl transferase, and
• the genetically modified microorganism being 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.

A method of in vivo acylation of a target peptide or protein in a genetically modified microorganism, comprising:

• expressing an acyl transferase encoded by a first gene;
• expressing a peptide or protein encoded by a second gene, one or both of the first and second gene being heterologous compared to a corresponding native microorganism;
• producing an acyl-CoA using a modified acyl-CoA biosynthetic pathway;
• and
• fermenting the microorganism under conditions effective 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,
• wherein either the acyl transferase is characterized by a mutation in an acyl-CoA binding site or the second gene is operatively linked to an oligonucleotide encoding a substrate for the acyl transferase.