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 or proteins/peptides, especially gut active proteins, without
purification is disclosed.