E. coli Recombinant Protein Production

Package Selection Guide

Our various E. coli protein production packages can start with an optional protein expression optimization study. We offer multiple scales of production up to 50 L, purification of both the soluable protein and inclusion body fractions and flexible QC analysis.

Popular packages

Features

Timeline

QC and Deliverable

Expression optimization

4-8 conditions

1 week

Expression report, soluble vs. insoluble fractions

Refolding screening

96 DWP, >200 conditions to choose

2-3 weeks

Refolding report

5 L, 10 L and 50 L (fermentation) Additional QC 1 L (shake flasks)

Fed batch RP-HPLC, bioburden, DSF, DSC, SPR, LC/MS, SEC-MALS, peptide mapping, cIEF, residual DNA, ELISA, Western blot, freeze thaw study, micro-developability testing Tag removal, biotinylation, endotoxin removal Concentration, Caliper (R/NR) or SDS-PAGE, LC/MS 4 weeks 3-4 weeks

Case Study: E. coli Expression Optimization

In this case study, we performed an expression optimization study to improve protein expression.

Key Challenge: Low expression

Expression condition optimization

Parameters

Original

Optimized

Medium Strain

Platform Medium BL21 (DE3) 20 1-5 24

Optimized Medium BL21 star (DE3) 37 >100 24

Expression Analysis

Final Products M 4 µg 4 µg P1 P2

Expression analysis

Final Products

37 50 75 100 150 250 kDa

100 150 250 kDa

E T S M

kDa M T S E

1 µg 2 µg 5 µg 10 µg

100 150 250 kDa

M

15 20 25 37 50 75 100 10 150 250

75 50 37 25 20 15 10

75 50 37 25 20 15 10

Temperature Titer (mg/L) Time (h)

Optimization

Target

Target

Target

15 20 25 10

Truncated

Case Study: MHC Production ɑ 2 ɑ 1 ɑ 2 ɑ 1 ɑ 2 ɑ 1 ɑ 2 ɑ 2 ɑ 1 ɑ 2

ɑ 1

ɑ 1

Over 260 MHC proteins produced from E. coli (0.1 L to 50 L)

+ +

+ +

+ +

Major histocompatibility complex (MHC) proteins are ternary complexes consisting of three components. They are notorisouly hard to express and assemble, while retaining the proper peptide presenting function. MHC Complex HLA B2M Peptide MHC Biotinylation ɑ 3 ɑ 3 MHC Complex HLA B2M Peptide MHC Biotinylation ɑ 3 ɑ 3 MHC Complex HLA B2M Peptide MHC Biotinylation ɑ 3 ɑ 3

Purification

Purification

Purification

ɑ 2 ɑ 2

ɑ 1 ɑ 1

ɑ 2 ɑ 2

ɑ 1 ɑ 1

ɑ 2

ɑ 2

ɑ 1

ɑ 1

ɑ 2

ɑ 2

ɑ 1

ɑ 1

ɑ 2

ɑ 1

ɑ 2

ɑ 1

MHC Biotinylation MHC Biotinylation Biotinylation MHC Biotinylation MHC Biotinylation

Purification Purification Purification Purification Purification

+ + + +

ɑ

ɑ 3 ɑ 3

ɑ 3

ɑ

ɑ 3

ɑ 3

3 ɑ

ɑ 3

3

ɑ

3

3

HLA B2M Peptide HLA B2M Peptide HLA B2M Peptide HLA B2M Peptide

MHC Complex MHC Complex MHC Complex MHC Complex MHC Complex

Purification Profile Purification Profile

Mass Spectrum Mass Spectrum

Final Product

Purification Profile

Purification Profile

Mass Spectrum

Mass Spectrum

Final Product

M 1µg 2µg 5µg 10µg Final Product Final Product

3 x10

3 x10

3 x10

2 x10

2 x10

2 x10

M 1µg 2µg 5µg 10µg

M 1µg 2µg 5µg 10µg

mAU

mAU

mAU

+ESI Scan (4.497-5.723 min, 74 Scans) Frag=200.0V H2-Db-1.d Subtr +ESI Scan (4.497-5.723 min, 74 Scans) Frag=200.0V H2-Db-1.d Subtr +ESI Scan (4.497-5.723 min, 74 Scans) Frag=200.0V H2-Db-1.d Subtr Purification Profile

+ESI Scan (4.497-5.723 min, 74 Scans) Frag=200.0V H2-Db-1.d Subtr +ESI Scan (4.497-5.723 min, 74 Scans) Frag=200.0V H2-Db-1.d Subtr +ESI Scan (4.497-5.723 min, 74 Scans) Frag=200.0V H2-Db-1.d Subtr

Mass Spectrum Mass Spectrum Mass Spectrum Mass Spectrum Mass Spectrum

Purification Profile Purification Profile Purification Profile Purification Profile

3 x10

Q HP Gradient

Q HP Gradient

Q HP Gradient

2 x10 2 x10

mAU 37421.48 mAU mAU mAU mAU

3000 2500 2000 1500 1000 500 0

3000 2500 2000 1500 1000 500 0

3000 2500 2000 1500 1000 500 0

+ESI Scan (4.497-5.723 min, 74 Scans) Frag=200.0V H2-Db-1.d Subtr +ESI Scan (4.497-5.723 min, 74 Scans) Frag=200.0V H2-Db-1.d Subtr +ESI Scan (4.497-5.723 min, 74 Scans) Frag=200.0V H2-Db-1.d Subtr +ESI Scan (4.497-5.723 min, 74 Scans) Frag=200.0V H2-Db-1.d Subtr +ESI Scan (4.497-5.723 min, 74 Scans) Frag=200.0V H2-Db-1.d Subtr

+ESI Scan (4.497- +ESI Scan (4.49 +ESI Scan (4.497 +ESI Scan (4.497-5 +ESI Scan (4.497-5

3 x10 1027.4328 3 x10 3 x10

2 x10

2 x10

37421.48

37421.48

1027.4328

1027.4328

0 1 2 3 4 5

0 1 2 3 4 5

0 1 2 3 4 5

8

8

8

2 x10

3 x10 Peptide

Peptide

Peptide

Q HP Gradient

3000 2500 2000 1500 1000 500 0 3000 2500 2000 1500 1000 500 0

Q HP Gradient Q HP Gradient Q HP Gradient 6 Q HP Gradient 6 6

37421.48 37421.48 37421.48 37421.48 37421.48

3000 2500 2000 1500 1000 500 0

3000 2500 2000 1500 1000 500 0

10 10

0 1 2 3 4 5

8

3000 2500 2000 1500 1000 500 0

10 1 1

0 1 2 3 4 5

0 1 2 3 4 5

8

8

0 1 2 3 4 5

8

HLDb Biotinylated

HLDb Biotinylated

HLDb Biotinylated

0 1 2 3 4 5

8

B2M

B2M

B2M

6

1028.4333

1028.4333

1028.4333

4

4

4

6

6

HLDb Biotinylated HLDb Biotinylated HLDb Biotinylated HLDb Biotinylated HLDb Biotinylated

6

6

B2M

B2M B2M 1029.4316

B2M 1029.4316

4

1029.4316

4

4

2

2

2

11861.29

11861.29

11861.29

4

4

2

11861.29 11861.29 11861.29 11861.29 11861.29

2

2

0

0

0

2

mL 700

mL

mL

2

0

0

0

100

100

100

200

200

200

300

300

300

400

400

400

500

500

500

600

600

600

700

700

10000 20000 30000 40000 50000 60000 70000 80000 90000 10000 20000 30000 40000 50000 60000 70000 80000 90000 10000 20000 30000 40000 50000 60000 70000 80000 90000

1026 1027 1028 1029 1030 1031 1032 1026 1027 1028 1029 1030 1031 1032 1026 1027 1028 1029 1030 1031 1032

0

mL mL

0

0

0

mL

mL

100 100

200 200

300 300

400 400

500 500

600 600

700 700

mL

10000 20000 30000 40000 50000 60000 70000 80000 90000 10000 20000 30000 40000 50000 60000 70000 80000 90000 10000 20000 30000 40000 50000 60000 70000 80000 90000 10000 20000 30000 40000 50000 60000 70000 80000 90000 Counts vs. Mass-to-Charge (m/z) 10000 20000 30000 40000 50000 60000 70000 80000 90000

1026 102 1026 10 1026 102 1026 1027 Co 1026 1027

0

200 Counts vs. Mass-to-Charge (m/z)

100 Counts vs. Mass-to-Charge (m/z)

300 Counts vs. Mass-to-Charge (m/z) 0 300 200 100 0

700 Counts vs. Mass-to-Charge (m/z) 600 600

700 Counts vs. Mass-to-Charge (m/z)

Counts vs. Mass-to-Charge (m/z)

400

400

500

500

0

100

200

300

400

500

600

700

0

Counts vs. Mass-to-Charge (m/z) Counts vs. Mass-to-Charge (m/z) Counts vs. Mass-to-Charge (m/z) Counts vs. Mass-to-Charge (m/z)

Co C C

Co

Learn more: Protein Sciences: Early-Stage R&D E. coli Platform

About WuXi Biologics

WuXi Biologics is a leading contract research, development and manufacturing organization (CRDMO) that provides end-to-end capabilities to healthcare organizations worldwide. With operations in China, the United States, Ireland, Germany, and Singapore, we enable our partners to effectively and efficiently bring biologics and vaccines to patients worldwide through our comprehensive and high-quality drug development model.

The world’s leading global single-source platform from concept to commercialization.

wuxibiologics.com | info@wuxibiologics.com

5-1-2024

Powered by