IP Library Granted Patent US 11,365,225
Granted Patent B2
US 11,365,225 · App. 15/776,998 · Granted Jun 21, 2022

Method of making recombinant silk and silk-amyloid hybrid proteins using bacteria

Inventors: Neel Satish Joshi (Somerville, MA); Peter Quoc Nguyen (Malden, MA)
C07K14/43518C07K14/47C07K14/78C07K2319/036C07K2319/10C12N1/205C12R2001/19
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Quick Facts
Patent No.
US 11,365,225
App. No.
15/776,998
Granted
Jun 21, 2022
Kind
B2
Abstract

Methods of making recombinant secretion of silk and silk-amyloid proteins using bacteria are provided.

Claims (9)

1. A method of producing an engineered Escherichia coli ( E. coli ) bacterium comprising

introducing into an E. coli bacterium an exogenous nucleic acid encoding a recombinant protein comprising a Sec domain for periplasmic localization, an N22 domain for directing the recombinant protein to the outer membrane for secretion, and at least one silk fibroin domain comprising the amino acid sequence set forth in SEQ ID NO:3; wherein the E. coli bacterium has at least one genomic nucleic acid encoding a Type VIII polypeptide secretion system; and wherein the exogenous nucleic acid is under operation of a promoter to express the recombinant protein.

2. The method of claim 1 , wherein the polypeptide secretion system is a HlyA Type 1 secretion system.

3. The method of claim 1 , wherein the polypeptide secretion system includes a periplasmic secretion system and a system for secretion through the outer membrane of the bacterium.

4. The method of claim 1 , wherein the polypeptide secretion system includes a periplasmic secretion system and a system for secretion through the outer membrane of the bacterium and the domain for periplasmic localization is a Tat domain or a signal recognition particle domain.

5. The method of claim 1 , wherein the polypeptide secretion system includes a periplasmic secretion system and a system for secretion through the outer membrane of the bacterium and wherein the domain for directing the recombinant protein to the outer membrane for secretion is a YebF domain.

6. The method of claim 1 , wherein the exogenous nucleic acid further encodes the recombinant protein to include a CsgA domain.

7. The method of claim 1 , wherein the silk fibroin domain comprises 4 to 64 repeats of the amino acid sequence set forth in SEQ ID NO:3.

8. The method of claim 1 , wherein the exogenous nucleic acid further encodes the recombinant protein to include one or more functional proteins comprising an enzyme, an antibody or a detectable protein.

Assignments (2)
CONFIRMATORY LICENSE Recorded May 20, 2024
From: HARVARD UNIVERSITY
To: PATENT ASSISTANT
Reel/Frame 067464/0403 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 2, 2019
From: JOSHI, NEEL SATISH; NGUYEN, PETER Q.
To: PRESIDENT AND FELLOWS OF HARVARD COLLEGE
Reel/Frame 047879/0390 →
Continuity (2)
Provisional Application 62257405 · Nov 19, 2015
Related Publication 20200291078A1 · Sep 17, 2020