For the full version, read the April 2023 edition of C&T.
Collagen is the most abundant protein in the human body and present in connective tissues such as cartilage, bones, tendons, ligaments and skin.1 The collagen superfamily comprises 28 members, of which type I collagen is the most abundant form (~80-85% of total collagen). Also a major protein in the extracellular matrix (ECM) of human cells, collagen I assembles into fibers that form the structural and mechanical scaffold (matrix) of skin and other connective tissues.
Collagen type III is the second most abundant collagen (~10-15% of total collagen) that is primarily produced by young fibroblasts before the tougher type I collagen is synthesized.2 Collagen III is found in granulation tissue as well as in artery walls, skin, intestines and the uterus.3-5
Both collagen I and III are fibrillar collagens that form higher order structures (fibrils, fibers and bundles) but they have slightly different structural properties. Type I collagen tends to form densely packed fibrils and a rigid triple helix for structure building. On the other hand, type III collagen forms a more flexible triple helical structure that assembles into small fibrils that are associated with the more rigid collagen I fibrils. As a result, collagen III functions as a modulator of overall tissue elasticity and function. Indeed, the ratio of collagen I/III correlates with skin aging and elasticity.6-9
Type I collagen is frequently used as a supplement in cosmetic products. While most commercial forms are derived from mammals such as bovine or porcine, other animal sources such chicken, fish skin and jellyfish have also been reported.10-16 Although animal-derived collagen is generally abundant and relatively inexpensive, it can suffer drawbacks such as the risk of infectious disease transmission, potential viral vector transmission from animal to human, allergenicity and unpleasant smell and color.17 Non-type I collagens, such as type III collagen, tend to be scarcer and more expensive due to the challenges of sourcing sufficient protein quantities and purifying them from natural sources.18
In the last two decades, with the advent of and advancement of genetic and cellular engineering, progressively more effort has been put into recombinant collagen production. Recombinant collagen molecules of different sizes have been expressed in all major platforms including mammalian cells, insect cells, yeast, bacteria and plant cells.19-37 In general, high quality, full-length collagen proteins have been produced in eukaryotic hosts but with low productivity.
Prokaryotic hosts such as E. coli have also been explored for the production of unmodified collagen although these recombinant proteins are generally either very small (a few kDa up to 20 kDa) or have been extensively modified from wild-type human collagen sequences. It is well-known that prokaryotic hosts lack the post-translational modification functions needed to generate the hydroxyproline amino acid residues found in mature animal-derived collagen. As such, previously produced recombinant collagen proteins generally only exhibit an unmodified collagen sequence.38-40
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