Abstract DNA sequences encoding proteins processable by secretion leaders in recombinant hosts are described. The DNA sequences encode the NH 2 -terminal region of proteins that are cleaved from a secretion leader and may be secreted through the cell membrane and, if present, cell wall in some cases. Proteins encoded by the DNA sequence have an NH 2 -terminal amino acid sequence conforming to a consensus amino acid sequence that is processable by the particular secretion leader. DNA sequences encoding a consensus amino acid sequence processable by the diphterhia toxin secretion leader are disclosed. A novel Pseudomonas exotoxin and CSF-1 having NH 2 -terminal sequences conforming to a consensus sequence are exemplified.
DNA comprising a DNA sequence encoding a mature protein heterologous to a DT leader sequence with an NH 2 terminal consensus sequence comprising about 7 amino acids having substantial homology to the first 7 amino terminal amino acids of mature DT wherein said mature protein is Pseudomonas exotoxin A having a glycine NH 2 -terminal in addition to the coding sequence of Pseudomonas exotoxin A.
Claim 2
Dependent Claim
65 words
DNA comprising a DNA sequence encoding a mature protein heterologous to a DT leader sequence with an NH 2 terminal consensus sequence comprising about 7 amino acids having substantial homology to the first 7 amino terminal amino acids of mature DT wherein said mature protein is Pseudomonas exotoxin A having a glycine NH 2 -terminal in addition to the coding sequence of Pseudomonas exotoxin A.
Claim 3
Dependent Claim
18 words
The DNA sequence of claim 1 wherein said Pseudomonas exotoxin A has the NH 2 -terminal sequence gly-ala-glu-glu-ala-phe-asp.
Claim 4
Dependent Claim
26 words
The DNA sequence of claim 8 wherein said mature protein is CSF-1 having gly-ala NH 2 -terminal in addition to the coding sequence of mature CSF-1.
Claim 5
Dependent Claim
19 words
The DNA sequence of claim 3 wherein said mature protein is CSF-1 having the NH 2 -terminal sequence gly-ala-glu-glu-val.
Claim 6
Dependent Claim
22 words
An expression vector comprising a DNA sequence encoding the DT leader sequence in reading frame with the DNA sequence of claim 1.
Claim 7
Dependent Claim
22 words
An expression vector comprising a DNA sequence encoding the DT leader sequence in reading frame with the DNA sequence of claim 3.
Claim 8
Dependent Claim
22 words
The expression vector of claim 5 wherein the DNA sequence encoding the NH 2 -terminal acid of the DT leader is ATG.
Claim 9
Dependent Claim
24 words
The expression vector of claim 6 wherein the DNA sequence encoding the NH 2 -terminal amino acid sequence of the DT leader is ATG.
Claim 10
Dependent Claim
11 words
A host organism transformed with the expression vector of claim 5.
Claim 11
Dependent Claim
11 words
A host organism transformed with the expression vector of claim 6.
Claim 12
Dependent Claim
11 words
A host organism transformed with the expression vector of claim 7.
Claim 13
Dependent Claim
11 words
A host organism transformed with the expression vector of claim 8.