Recombinant microbial systems for the production of human collagen and gelatin.
The use of genetically engineered microorganisms is a cost-effective, scalable technology for the production of recombinant human collagen (rhC) and recombinant gelatin (rG). This review will discuss the use of yeast (Pichia pastoris, Saccharomyces cerevisiae, Hansenula polymorpha) and of bacteria (Escherichia coli, Bacillus brevis) genetically engineered for the production of rhC and rG. P. pastoris is the preferred production system for rhC and rG. Recombinant strains of P. pastoris accumulate properly hydroxylated triple helical rhC intracellularly at levels up to 1.5 g/l. Coexpression of recombinant collagen with recombinant prolyl hydroxylase results in the synthesis of hydroxylated collagen with thermal stability similar to native collagens. The purified hydroxylated rhC forms fibrils that are structurally similar to fibrils assembled from native collagen. These qualities make rhC attractive for use in many medical applications. P. pastoris can also be engineered to secrete high levels (3 to 14 g/l ) of collagen fragments with defined length, composition, and physiochemical properties that serve as substitutes for animal-derived gelatins. The replacement of animal-derived collagen and gelatin with rhC and rG will result in products with improved safety, traceability, reproducibility, and quality. In addition, the rhC and rG can be engineered to improve the performance of products containing these biomaterials.
Báez
Julio
J
FibroGen, Inc., 225 Gateway Boulevard, South San Francisco, CA 94080, USA. jbaez@fibrogen.com
Olsen
David
D
Polarek
James W
JW
D001709:Biotechnology / Q000379:methods; D003094:Collagen / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D005780:Gelatin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D010843:Pichia / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis* / Q000235:genetics
D011994:Recombinant Proteins; D005780:Gelatin; D003094:Collagen