Granted Patent
B2
US 12,258,605 · App. 17/560,753 · Granted Mar 25, 2025
Alkane oxidation by modified hydroxylases
Inventors:
Frances Arnold (Pasadena, CA); Peter Meinhold (Pasadena, CA); Matthew W. Peters (Pasadena, CA); Rudi Fasan (Brea, CA); Mike M. Y. Chen (Pasadena, CA)
Assignee:
California Institute of Technology
C12P7/04C07K14/32C12N9/0042C12N9/0071C12N9/0077C12P7/06C12Y106/02004C12Y114/14001C12Y114/15C12Y114/15003Y02E50/10Y02P20/52
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Abstract
This invention relates to modified hydroxylases. The invention further relates to cells expressing such modified hydroxylases and methods of producing hydroxylated alkanes by contacting a suitable substrate with such cells.
Claims (18)
1. An isolated or recombinant polypeptide comprising residues 456-1048 of the amino acid sequence set forth in SEQ ID NO: 1 with up to 65 conservative amino acid substitutions excluding residues 464, 631, 645, 710 and 968, wherein the amino acid sequence comprises residues selected from the group consisting of:
(a) at position 464, a Z1, Z3, Z4, or Z5 amino acid residue;
(b) at positions 631 and 710, a Z1 amino acid residue;
(c) at position 645, a Z3 amino acid residue; and
(d) at position 968, a Z2 amino acid residue,
wherein: Z1 is an amino acid residue selected from the group consisting of glycine (G), asparagine (N), glutamine (Q), serine(S), threonine (T), tyrosine (Y), and cysteine (C); Z2 is an amino acid residue selected from the group consisting of alanine (A), valine (V), leucine (L), isoleucine (I), proline (P), and methionine (M); Z3 is an amino acid residue selected from the group consisting of lysine (K), and arginine (R); Z4 is an amino acid residue selected from the group consisting of tyrosine (Y), phenylalanine (F), tryptophan (W), and histidine (H); and is an amino acid residue selected from the group consisting of threonine (T), valine (V), and isoleucine (I), wherein when the isolated or recombinant polypeptide is operably linked to the heme domain of a cytochrome P450 enzyme to form a chimeric polypeptide the chimeric polypeptide has cytochrome P450 activity.
2. The polypeptide of claim 1 , comprising up to 40 conservative amino acid substitutions excluding residues 464, 631, 645, 710 and 968 of SEQ ID NO: 1.
3. The polypeptide of claim 1 , comprising up to 25 conservative amino acid substitutions excluding residues 464, 631, 645, 710 and 968 of SEQ ID NO: 1.
4. The polypeptide of claim 1 , comprising up to 10 conservative amino acid substitutions excluding residues 464, 631, 645, 710 and 968 of SEQ ID NO: 1.
5. The polypeptide of claim 1 , wherein the amino acid sequence comprises residues selected from the group consisting of:
(a) at position 464, a glycine (G), arginine (R), tyrosine (Y), or threonine (T) amino acid residue;
(b) at position 631, an asparagine (N) amino acid residue;
(c) at position 645, an arginine (R) amino acid residue;
(d) at position 710, a threonine (T) amino acid residue; and
(e) at position 968, a lysine (L) amino acid residue.
6. The polypeptide of claim 1 , comprising up to 50 conservative amino acid substitutions excluding residues 464, 631, 645, 710 and 968 of SEQ ID NO:1.
7. A chimeric polypeptide comprising the isolated or recombinant polypeptide of claim 1 , operably linked to a heme catalytic domain, wherein the chimeric polypeptide has cytochrome P450 activity.
8. The chimeric polypeptide of claim 7 , wherein the heme catalytic domain is from a species different than the isolated or recombinant polypeptide.
Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jul 24, 2024
From: ARNOLD, FRANCES; MEINHOLD, PETER; PETERS, MATTHEW W.; FASAN, RUDI; CHEN, MIKE M.Y.
To: CALIFORNIA INSTITUTE OF TECHNOLOGY
Reel/Frame 068073/0671 →
SECURITY INTEREST
Recorded Feb 15, 2024
From: CODEXIS, INC.
To: INNOVATUS LIFE SCIENCES LENDING FUND I, LP, AS COLLATERAL AGENT
Reel/Frame 066600/0650 →
Continuity (12)
Continuation In Part
PCTUS2006011273
· Mar 28, 2006
Provisional Application
60900243
· Feb 8, 2007
Provisional Application
60700781
· Jul 20, 2005
Provisional Application
60698872
· Jul 13, 2005
Provisional Application
60665903
· Mar 28, 2005
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