Micro-algae come of age as a platform for recombinant protein production

Abstract

A complete set of genetic tools is still being developed for the micro-alga Chlamydomonas reinhardtii. Yet even with this incomplete set, this photosynthetic single-celled plant has demonstrated significant promise as a platform for recombinant protein expression. In recent years, techniques have been developed that allow for robust expression of genes from both the nuclear and plastid genome. With these advances, many research groups have examined the pliability of this and other micro-algae as biological machines capable of producing recombinant peptides and proteins. This review describes recent successes in recombinant protein production in Chlamydomonas, including production of complex mammalian therapeutic proteins and monoclonal antibodies at levels sufficient for production at economic parity with existing production platforms. These advances have also shed light on the details of algal protein production at the molecular level, and provide insight into the next steps for optimizing micro-algae as a useful platform for the production of therapeutic and industrially relevant recombinant proteins.

Fig. 1

Chlamydomonas reinhardtii as a versatile recombinant protein production platform. Protein expressed from the chloroplast genome is accumulated inside the single large chloroplast (a). The reducing environment of the chloroplast allows for proper folding of heavily disulfide bonded proteins, which is not easily accomplished in bacterial production platforms. Protein expressed from the nuclear genome accumulates in the cytosol (b), unless it is given an export signal sequence. In this case, it is sent to the endoplasmic reticulum for translocation and processing and then moves to the Golgi apparatus for packaging and export to the extracellular media (c)