Methods and compositions are disclosed to engineer chloroplast comprising heterologous mammalian genes via a direct replacement of chloroplast Photosystem II (PSII) reaction center protein coding regions to achieve expression of recombinant protein above 5% of total protein. When algae is used, algal expressed protein is produced predominantly as a soluble protein where the functional activity of the peptide is intact. As the host algae is edible, production of biologics in this organism for oral delivery of proteins/peptides, especially gut active proteins, without purification is disclosed.
This invention was made with government support under Grant Nos. RO1 GM054659-08 and 5RO1 AI059614-02 awarded by the National Institutes of Health and Grant No. DEFG0302ER15313 awarded by the Department of Energy. The government has certain rights in this invention.