Biosynthetic Pathway for Heterologous Expression of a Nonribosomal Peptide Synthetase Drug and Analogs
AssigneesThe Regents of the University of Michigan, Clorado State University Research Foundation, Allegheny-Singer Research Institute
InventorsDavid H. Sherman, Garth D. Ehrlich, Benjamin Janto, Robert M. Williams, Christopher M. Rath
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Abstract
The present invention is directed to the biosynthetic pathway for a nonribosomal peptide synthetase (NRPS) derived drug and analogs thereof. The invention also discloses polynucleotide sequences useful for heterologous expression in a convenient microbial host for the synthesis of the NRPS derived drug.
Claims24
A host cell transformed with a polynucleotide encoding (i) EtuA1 (SEQ ID NO:
- 1) or a protein 95% identical to SEQ ID NO:
- 1 having EtuA1 activity, and (ii) EtuA2 (SEQ ID NO:
- 2) or a protein 95% identical to SEQ ID NO:
- 2 having EtuA2 activity.
A host cell transformed with a polynucleotide encoding EtuO (SEQ ID NO:
- 16) or a protein 95% identical to SEQ ID NO:
- 16 having EtuO activity.
16-40. (canceled)
A polynucleotide encoding the protein of claim 48.
(canceled)
(canceled)
(canceled)
(canceled)
(canceled)
A protein comprising an amino acid sequence that is selected from the group consisting of the sequence set out in:
- (i) SEQ ID NO:
- 1 or a protein 95% identical to SEQ ID NO:
- 1 having EtuA1 activity;
- (ii) SEQ ID NO:
- 2 or a protein 95% identical to SEQ ID NO:
- 2 having EtuA2 activity;
- (iii) SEQ ID NO:
- 3 or a protein 95% identical to SEQ ID NO:
- 3 having EtuA3 activity;
- (iv) SEQ ID NO:
- 4 or a protein 95% identical to SEQ ID NO:
- 4 having EtuD1 activity;
- (v) SEQ ID NO:
- 5 or a protein 95% identical to SEQ ID NO:
- 5 having EtuD2 activity;
- (vi) SEQ ID NO:
- 6 or a protein 95% identical to SEQ ID NO:
- 6 having EtuD3 activity;
- (vii) SEQ ID NO:
- 7 or a protein 95% identical to SEQ ID NO:
- 7 having EtuF1 activity;
- (viii) SEQ ID NO:
- 8 or a protein 95% identical to SEQ ID NO:
- 8 having EtuF2 activity;
- (ix) SEQ ID NO:
- 9 or a protein 95% identical to SEQ ID NO:
- 9 having EtuF3 activity;
- (x) SEQ ID NO:
- 10 or a protein 95% identical to SEQ ID NO:
- 10 having EtuH activity;
- (xi) SEQ ID NO:
- 11 or a protein 95% identical to SEQ ID NO:
- 11 having EtuM1 activity;
- (xii) SEQ ID NO:
- 12 or a protein 95% identical to SEQ ID NO:
- 12 having EtuM2 activity;
- (xiii) SEQ ID NO:
- 13 or a protein 95% identical to SEQ ID NO:
- 13 having EtuN1 activity;
- (xix) SEQ ID NO:
- 14 or a protein 95% identical to SEQ ID NO:
- 14 having EtuN2 activity;
- (xx) SEQ ID NO:
- 15 or a protein 95% identical to SEQ ID NO:
- 15 having EtuN3 activity;
- (xxi) SEQ ID NO:
- 16 or a protein 95% identical to SEQ ID NO:
- 16 having EtuO activity;
- (xxii) SEQ ID NO:
- 17 or a protein 95% identical to SEQ ID NO:
- 17 having EtuP1 activity;
- (xxiii) SEQ ID NO:
- 18 or a protein 95% identical to SEQ ID NO:
- 18 having EtuP2 activity;
- (xxiv) SEQ ID NO:
- 19 or a protein 95% identical to SEQ ID NO:
- 19 having EtuR1 activity
- (xxv) SEQ ID NO:
- 20 or a protein 95% identical to SEQ ID NO:
- 20 having EtuR2 activity;
- (xxvi) SEQ ID NO:
- 21 or a protein 95% identical to SEQ ID NO:
- 21 having EtuR3 activity;
- (xxvii) SEQ ID NO:
- 22 or a protein 95% identical to SEQ ID NO:
- 22 having EtuT activity;
- (xxviii)SEQ ID NO:
- 23 or a protein 95% identical to SEQ ID NO:
- 23 having EtuU1 activity;
- (xxix) SEQ ID NO:
- 24 or a protein 95% identical to SEQ ID NO:
- 24 having EtuU2 activity;
- and
- (xxx) SEQ ID NO:
- 25 or a protein 95% identical to SEQ ID NO:
- 25 having EtuU3 activity.
Dependencies are inferred from the claim text.