A system for production of commercial quantities of human lactoferrin: a broad spectrum natural antibiotic.
We previously reported the production of limited quantities of biologically active recombinant human lactoferrin in the filamentous fungus Aspergillus oryzae. In the present study, we report a modification of this production system combined with a classical strain improvement program that has enabled production of levels of recombinant human lactoferrin in excess of 2 g/l. The protein was expressed in Aspergillus awamori as a glucoamylase fusion polypeptide which was secreted into the growth medium and processed to mature human lactoferrin by an endogenous KEX-2 peptidase. The recombinant protein retains full biological activity in terms of its ability to bind iron and human enterocyte receptors. Furthermore, the recombinant protein functions as a potent broad spectrum antimicrobial protein.
Ward
P P
PP
Department of Cell Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Piddington
C S
CS
Cunningham
G A
GA
Zhou
X
X
Wyatt
R D
RD
Conneely
O M
OM
D000818:Animals; D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000494:pharmacology; D001230:Aspergillus; D018938:Caco-2 Cells; D004926:Escherichia coli / Q000187:drug effects; D005260:Female; D005087:Glucan 1,4-alpha-Glucosidase / Q000235:genetics; D006031:Glycosylation; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007781:Lactoferrin / Q000096:biosynthesis* / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D008826:Microbial Sensitivity Tests; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis* / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D011993:Recombinant Fusion Proteins; D005087:Glucan 1,4-alpha-Glucosidase; D007781:Lactoferrin