scholarly journals Equivalent Recombinant Human Insulin Preparations and their Place in Therapy

2015 ◽  
Vol 11 (1) ◽  
pp. 10 ◽  
Author(s):  
Juergen Sandow ◽  
Wolfgang Landgraf ◽  
Reinhard Becker ◽  
Gerhard Seipke ◽  
◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Saccharomyces Cerevisiae ◽  
Human Insulin ◽  
Regulatory Approval ◽  
Brand Names ◽  
Recombinant Human Insulin ◽  
Commercial Development ◽  
Euglycaemic Clamp

Recombinant human insulin was one of the first products of biotechnology. It was developed in response to the need for a consistent and sufficient worldwide supply. Recombinant human insulin replaced the animal insulins and semisynthetic insulins obtained by modification of animal insulins. Bioequivalence studies were required for regulatory approval. Three reference products were independently established during these procedures: Humulin® (Eli Lilly and Co), Novolin® (NovoNordisk) and Insuman® (Sanofi). Numerous brand names have been used during the commercial development of recombinant human insulin formulations. In this review, three current brand names are used for consistent identification. Human insulin for Humulin and Insuman are produced by fermentation in bacteria (Escherichia coli) and for Novolin in yeast (Saccharomyces cerevisiae). The bioequivalence of recombinant human insulin products was investigated in euglycaemic clamp studies. An overview of such bioequivalence studies is provided here. This paper will consider the relevance of human insulin formulations today and their place in therapy.

scholarly journals Improved Secretion of Native Human Insulin-Like Growth Factor 1 from gas1 Mutant Saccharomyces cerevisiae Cells

2000 ◽  
Vol 66 (12) ◽  
pp. 5477-5479 ◽  
Author(s):  
Marina Vai ◽  
Luca Brambilla ◽  
Ivan Orlandi ◽  
Nicola Rota ◽  
Bianca Maria Ranzi ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Growth Factor ◽  
Human Insulin ◽  
Considerable Increase ◽  
Yeast Cells ◽  
Host Strain ◽  
Insulin Like Growth Factor ◽  
Recombinant Human Insulin ◽  
Factor Α ◽  
Mating Factor

ABSTRACT We studied the secretion of recombinant human insulin-like growth factor 1 (rhIGF-1) from transformed yeast cells. The hIGF-1gene was fused to the mating factor α prepro- leader sequence under the control of the constitutive ACT1 promoter. We found that the inactivation of the GAS1 gene in the host strain led to a supersecretory phenotype yielding a considerable increase, from 8 to 55 mg/liter, in rhIGF-1 production.

Recombinant Human Insulin-Like Growth Factor II Expressed in Escherichia coli

1987 ◽  
Vol 5 (10) ◽  
pp. 1047-1051 ◽  
Author(s):  
Thomas C. Furman ◽  
Janet Epp ◽  
Hansen M. Hsiung ◽  
JoAnn Hoskins ◽  
George L. Long ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Growth Factor ◽  
Human Insulin ◽  
Insulin Like Growth Factor ◽  
Recombinant Human Insulin ◽  
Factor Ii

scholarly journals Separation and characterization of modified variants of recombinant human insulin-like growth factor I derived from a fusion protein secreted from Escherichia coli

1990 ◽  
Vol 271 (2) ◽  
pp. 357-363 ◽  
Author(s):  
G Forsberg ◽  
G Palm ◽  
A Ekebacke ◽  
S Josephson ◽  
M Hartmanis
Keyword(s):  
Escherichia Coli ◽  
Growth Factor ◽  
Fusion Protein ◽  
Human Insulin ◽  
Insulin Like Growth Factor ◽  
Recombinant Human Insulin ◽  
Factor I ◽  
Methionine Residue ◽  
Igf I ◽  
Growth Factor I

Human insulin-like growth factor I, IGF-I, was produced in Escherichia coli fused to a synthetic IgG-binding peptide The fusion protein is secreted into the medium during fermentation and was initially purified on an IgG-Sepharose column. After hydroxylamine cleavage, IGF-I was purified to homogeneity. During purification, impurities in the form of modified variants of IGF-I were detected and characterized. The closely related impurities were identified to be a misfolded form of IGF-I, having mismatched disulphide bonds, a form with the single methionine residue in IGF-I oxidized to methionine sulphoxide and a variant in which the methionine residue was substituted by a norleucine residue during protein synthesis. A form proteolytically cleaved between two arginine residue was also detected. These impurities were separated from the major component, native IGF-I, by using reverse-phase h.p.l.c. The modified molecules as well as native IGF-I were characterized both as intact molecules and as fragments, after pepsin digestion, using the techniques of plasma desorption m.s., N-terminal sequencing and amino acid analysis. The oxidized form was 90%, and the norleucine analogue was 70%, as potent as native IGF-I in a biological radioreceptor assay, and the form having mismatched disulphides lacked receptor affinity.

Microbe Engineering of Guaia-6,10(14)-diene as a Building Block for the Semisynthetic Production of Plant-Derived (−)-Englerin A

2019 ◽  
Author(s):  
Thomas Siemon ◽  
Zhangqian Wang ◽  
Guangkai Bian ◽  
Tobias Seitz ◽  
Ziling Ye ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Saccharomyces Cerevisiae ◽  
Synthetic Biology ◽  
Chemical Synthesis ◽  
Building Block ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Economical Method ◽  
Englerin A ◽  
Transient Receptor

Herein, we report the semisynthetic production of the potent transient receptor potential canonical (TRPC) channel agonist (−)-englerin A (EA), using guaia-6,10(14)-diene as the starting material. Guaia-6,10(14)-diene was systematically engineered in Escherichia coli and Saccharomyces cerevisiae using the CRISPR/Cas9 system and produced with high titers. This provided us the opportunity to execute a concise chemical synthesis of EA and the two related guaianes (−)-oxyphyllol and (+)-orientalol E. The potentially scalable approach combines the advantages of synthetic biology and chemical synthesis and provides an efficient and economical method for producing EA as well as its analogs.

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