Downstream processing of recombinant human insulin and its analogues production from E. coli inclusion bodies

Abstract The Global Diabetes Compact was launched by the World Health Organization in April 2021 with one of its important goals to increase the accessibility and affordability of life-saving medicine—insulin. The rising prevalence of diabetes worldwide is bound to escalate the demand for recombinan...

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Main Authors: Yin Yin Siew, Wei Zhang
Format: Article
Language:English
Published: SpringerOpen 2021-07-01
Series:Bioresources and Bioprocessing
Subjects:
Online Access:https://doi.org/10.1186/s40643-021-00419-w
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spelling doaj-ace5fa9cd7d34233a0b521e727b15c0f2021-08-01T11:04:13ZengSpringerOpenBioresources and Bioprocessing2197-43652021-07-018112710.1186/s40643-021-00419-wDownstream processing of recombinant human insulin and its analogues production from E. coli inclusion bodiesYin Yin Siew0Wei Zhang1Downstream Processing Group, Bioprocessing Technology Institute, Agency for Science, Technology and ResearchDownstream Processing Group, Bioprocessing Technology Institute, Agency for Science, Technology and ResearchAbstract The Global Diabetes Compact was launched by the World Health Organization in April 2021 with one of its important goals to increase the accessibility and affordability of life-saving medicine—insulin. The rising prevalence of diabetes worldwide is bound to escalate the demand for recombinant insulin therapeutics, and currently, the majority of recombinant insulin therapeutics are produced from E. coli inclusion bodies. Here, a comprehensive review of downstream processing of recombinant human insulin/analogue production from E. coli inclusion bodies is presented. All the critical aspects of downstream processing, starting from proinsulin recovery from inclusion bodies, inclusion body washing, inclusion body solubilization and oxidative sulfitolysis, cyanogen bromide cleavage, buffer exchange, purification by chromatography, pH precipitation and zinc crystallization methods, proinsulin refolding, enzymatic cleavage, and formulation, are explained in this review. Pertinent examples are summarized and the practical aspects of integrating every procedure into a multimodal purification scheme are critically discussed. In the face of increasing global demand for insulin product, there is a pressing need to develop a more efficient and economical production process. The information presented would be insightful to all the manufacturers and stakeholders for the production of human insulins, insulin analogues or biosimilars, as they strive to make further progresses in therapeutic recombinant insulin development and production.https://doi.org/10.1186/s40643-021-00419-wRecombinant human insulinInsulin analoguesE. coli inclusion bodiesDownstream processingPurification
collection DOAJ
language English
format Article
sources DOAJ
author Yin Yin Siew
Wei Zhang
spellingShingle Yin Yin Siew
Wei Zhang
Downstream processing of recombinant human insulin and its analogues production from E. coli inclusion bodies
Bioresources and Bioprocessing
Recombinant human insulin
Insulin analogues
E. coli inclusion bodies
Downstream processing
Purification
author_facet Yin Yin Siew
Wei Zhang
author_sort Yin Yin Siew
title Downstream processing of recombinant human insulin and its analogues production from E. coli inclusion bodies
title_short Downstream processing of recombinant human insulin and its analogues production from E. coli inclusion bodies
title_full Downstream processing of recombinant human insulin and its analogues production from E. coli inclusion bodies
title_fullStr Downstream processing of recombinant human insulin and its analogues production from E. coli inclusion bodies
title_full_unstemmed Downstream processing of recombinant human insulin and its analogues production from E. coli inclusion bodies
title_sort downstream processing of recombinant human insulin and its analogues production from e. coli inclusion bodies
publisher SpringerOpen
series Bioresources and Bioprocessing
issn 2197-4365
publishDate 2021-07-01
description Abstract The Global Diabetes Compact was launched by the World Health Organization in April 2021 with one of its important goals to increase the accessibility and affordability of life-saving medicine—insulin. The rising prevalence of diabetes worldwide is bound to escalate the demand for recombinant insulin therapeutics, and currently, the majority of recombinant insulin therapeutics are produced from E. coli inclusion bodies. Here, a comprehensive review of downstream processing of recombinant human insulin/analogue production from E. coli inclusion bodies is presented. All the critical aspects of downstream processing, starting from proinsulin recovery from inclusion bodies, inclusion body washing, inclusion body solubilization and oxidative sulfitolysis, cyanogen bromide cleavage, buffer exchange, purification by chromatography, pH precipitation and zinc crystallization methods, proinsulin refolding, enzymatic cleavage, and formulation, are explained in this review. Pertinent examples are summarized and the practical aspects of integrating every procedure into a multimodal purification scheme are critically discussed. In the face of increasing global demand for insulin product, there is a pressing need to develop a more efficient and economical production process. The information presented would be insightful to all the manufacturers and stakeholders for the production of human insulins, insulin analogues or biosimilars, as they strive to make further progresses in therapeutic recombinant insulin development and production.
topic Recombinant human insulin
Insulin analogues
E. coli inclusion bodies
Downstream processing
Purification
url https://doi.org/10.1186/s40643-021-00419-w
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