Cost-effective production of recombinant peptides in Escherichia coli

Rosa Gaglione, Katia Pane, Eliana Dell'Olmo, Valeria Cafaro, Elio Pizzo, Giuseppe Olivieri, Eugenio Notomista, Angela Arciello

Research output: Contribution to journalArticleAcademicpeer-review

1 Citation (Scopus)

Abstract

Among bioactive peptides, cationic antimicrobial peptides (AMPs), also referred to as host defence peptides (HDPs), are valuable tools to treat infections, being able to kill a wide variety of microbes directly and/or modulate host immunity. HDPs have great therapeutic potential against antibiotic-resistant bacteria, viruses and even parasites. However, high manufacturing costs have greatly limited their development as drugs, thus highlighting the need to develop novel and competitive production strategies. Here, a cost-effective procedure was established to produce the high amounts of peptides required for basic and clinical research. Firstly, a novel culture medium was designed, which was found to support significantly higher cell densities and recombinant expression levels of peptides under test compared to conventional media. The procedure has been also efficiently scaled up by using a 5 L fermenter, while the costs have been lowered significantly by developing a successful auto-induction strategy, which has been found to support higher yields of target constructs and cell biomass compared to conventional strategies based on expression induction by IPTG. Interestingly, it was estimated that by increasing production scale from 100 to 1000 mg/batch, unit costs decreased strongly from 253 to 42 €/mg. These costs appear highly competitive when compared to chemical synthesis strategies. Altogether, the data indicate that the strategy represents an important starting point for the future development of large-scale manufacture of HDPs.

LanguageEnglish
Pages39-48
Number of pages10
JournalNew Biotechnology
Volume51
DOIs
Publication statusPublished - 25 Jul 2019

Fingerprint

Escherichia coli
Peptides
Costs and Cost Analysis
Costs
Antimicrobial Cationic Peptides
Fermenters
Isopropyl Thiogalactoside
Viruses
Culture Media
Bacteria
Biomass
Antibiotics
Immunity
Anti-Bacterial Agents
Parasites
Cell Count
Pharmaceutical Preparations
Infection
Research

Keywords

  • Apolipoprotein A-I
  • Apolipoprotein B
  • Auto-inducing expression procedure
  • Cost-effective recombinant production
  • Host defence peptides
  • Techno-economic analysis

Cite this

Gaglione, R., Pane, K., Dell'Olmo, E., Cafaro, V., Pizzo, E., Olivieri, G., ... Arciello, A. (2019). Cost-effective production of recombinant peptides in Escherichia coli. New Biotechnology, 51, 39-48. https://doi.org/10.1016/j.nbt.2019.02.004
Gaglione, Rosa ; Pane, Katia ; Dell'Olmo, Eliana ; Cafaro, Valeria ; Pizzo, Elio ; Olivieri, Giuseppe ; Notomista, Eugenio ; Arciello, Angela. / Cost-effective production of recombinant peptides in Escherichia coli. In: New Biotechnology. 2019 ; Vol. 51. pp. 39-48.
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Gaglione, R, Pane, K, Dell'Olmo, E, Cafaro, V, Pizzo, E, Olivieri, G, Notomista, E & Arciello, A 2019, 'Cost-effective production of recombinant peptides in Escherichia coli', New Biotechnology, vol. 51, pp. 39-48. https://doi.org/10.1016/j.nbt.2019.02.004

Cost-effective production of recombinant peptides in Escherichia coli. / Gaglione, Rosa; Pane, Katia; Dell'Olmo, Eliana; Cafaro, Valeria; Pizzo, Elio; Olivieri, Giuseppe; Notomista, Eugenio; Arciello, Angela.

In: New Biotechnology, Vol. 51, 25.07.2019, p. 39-48.

Research output: Contribution to journalArticleAcademicpeer-review

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T1 - Cost-effective production of recombinant peptides in Escherichia coli

AU - Gaglione, Rosa

AU - Pane, Katia

AU - Dell'Olmo, Eliana

AU - Cafaro, Valeria

AU - Pizzo, Elio

AU - Olivieri, Giuseppe

AU - Notomista, Eugenio

AU - Arciello, Angela

PY - 2019/7/25

Y1 - 2019/7/25

N2 - Among bioactive peptides, cationic antimicrobial peptides (AMPs), also referred to as host defence peptides (HDPs), are valuable tools to treat infections, being able to kill a wide variety of microbes directly and/or modulate host immunity. HDPs have great therapeutic potential against antibiotic-resistant bacteria, viruses and even parasites. However, high manufacturing costs have greatly limited their development as drugs, thus highlighting the need to develop novel and competitive production strategies. Here, a cost-effective procedure was established to produce the high amounts of peptides required for basic and clinical research. Firstly, a novel culture medium was designed, which was found to support significantly higher cell densities and recombinant expression levels of peptides under test compared to conventional media. The procedure has been also efficiently scaled up by using a 5 L fermenter, while the costs have been lowered significantly by developing a successful auto-induction strategy, which has been found to support higher yields of target constructs and cell biomass compared to conventional strategies based on expression induction by IPTG. Interestingly, it was estimated that by increasing production scale from 100 to 1000 mg/batch, unit costs decreased strongly from 253 to 42 €/mg. These costs appear highly competitive when compared to chemical synthesis strategies. Altogether, the data indicate that the strategy represents an important starting point for the future development of large-scale manufacture of HDPs.

AB - Among bioactive peptides, cationic antimicrobial peptides (AMPs), also referred to as host defence peptides (HDPs), are valuable tools to treat infections, being able to kill a wide variety of microbes directly and/or modulate host immunity. HDPs have great therapeutic potential against antibiotic-resistant bacteria, viruses and even parasites. However, high manufacturing costs have greatly limited their development as drugs, thus highlighting the need to develop novel and competitive production strategies. Here, a cost-effective procedure was established to produce the high amounts of peptides required for basic and clinical research. Firstly, a novel culture medium was designed, which was found to support significantly higher cell densities and recombinant expression levels of peptides under test compared to conventional media. The procedure has been also efficiently scaled up by using a 5 L fermenter, while the costs have been lowered significantly by developing a successful auto-induction strategy, which has been found to support higher yields of target constructs and cell biomass compared to conventional strategies based on expression induction by IPTG. Interestingly, it was estimated that by increasing production scale from 100 to 1000 mg/batch, unit costs decreased strongly from 253 to 42 €/mg. These costs appear highly competitive when compared to chemical synthesis strategies. Altogether, the data indicate that the strategy represents an important starting point for the future development of large-scale manufacture of HDPs.

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KW - Host defence peptides

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JO - New Biotechnology

T2 - New Biotechnology

JF - New Biotechnology

SN - 1871-6784

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