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Abstract
The tools of recombinant protein expression are now being used to provide recombinant
sources of both collagen and gelatin. The primary focus of this review is to discuss
alternatives to bovine collagen for biomedical applications. Several recombinant systems
have been developed for production of human sequence collagens. Mammalian and insect
cells were initially used, but were thought to be too costly for commercial production.
Yeast have been engineered to express high levels of type I homotrimer and heterotrimer
and type II and type III collagen. Co-expression of collagen genes and cDNAs encoding
the subunits of prolyl hydroxylase has lead to the synthesis of completely hydroxylated,
thermostable collagens. Human types I and III collagen homotrimers have been expressed
in transgenic tobacco plants, while transgenic mice have been engineered to produce
full-length type I procollagen homotrimer as well as a alpha2 (I) homotrimeric mini-collagen.
Most recently, a transgenic silkworm system was used to produce a fusion protein containing
a collagenous sequence. Each of these transgenic systems holds great promise for the
cost-effective large-scale production of recombinant human collagens. As seen in other
recombinant expression systems, transgenic silkworms, tobacco, and mice lack sufficient
endogenous prolyl hydroxylase activity to produce fully hydroxylated collagen. In
mice and tobacco, this was overcome by over-expression of prolyl hydroxylase, analogous
to what has been done in yeast and insect cell culture. In addition to recombinant
alternatives to bovine collagen, other sources such as fish and sponge collagen are
discussed briefly. Recombinant gelatin has been expressed in Pichia pastoris and Hansenula
polymorpha in both non-hydroxylated and hydroxylated forms. Pichia was shown to be
a highly productive system for gelatin production. The recombinant gelatins produced
in yeast are of defined molecular weight and physio-chemical properties and represent
a new biomaterial not previously available from animal sources. Genetic engineering
has made great progress in the areas of recombinant collagen and gelatin expression,
and there are now several alternatives to bovine material that offer an enhanced safety
profile, greater reproducibility and quality, and the ability of these materials to
be tailored to enhance product performance.