Engineering algae for the production of therapeutic proteins and biofuels
The research in the Mayfield lab focuses on molecular genetics in green algae, and on the production of therapeutic proteins and biofuel molecules using algae as a production platform. To developed algae as a biotechnology platform we are developing the molecular tools that will be used to produce either recombinant proteins or engineered biofuel molecules. We have developed a number of expression vectors that allow for robust accumulation of complex mammalian proteins including monoclonal antibodies, mammalian growth factors, and a variety of potential industrial enzymes. We have shown that this algal-based system is capable of producing these recombinant proteins at very high levels. Recent studies have focused on producing antibody-toxin fusion proteins, in which a targeting antibody domain is linked to a cell-killing toxin. Using this technology we have produced an antibody-toxin fusion that binds and kills human B-cell lymphomas, and cell-based assays have demonstrated the utility and specificity of this molecule. These proteins have great potential for the treatment of cancers and infectious diseases, and chloroplasts offer perhaps the only system in which these types of proteins can be produced. We have also recently succeeded in generating expression vectors that allow for expression of recombinant proteins form the nuclear genome at relatively high levels, and that also allow for secretion of these proteins from the cell. These new vector will increase the repertoire of recombinant proteins that can be produced in algae thereby expanding the platform. Engineering algae for the production of hydrocarbon molecules that can be used as biofuels, is also a major focus of the lab, and recent studies have demonstrated the tremendous potential of eukaryotic algae for the expression of recombinant enzymes that allow for greater production of biofuels. Our continued genetic, biochemical and structural studies should lead to a greater understanding of the mechanism of gene expression in algae, and allow algae to become a viable source for sustainable biofuel and recombinant protein production.
Trans, M., Zhou, B., Mayfield. S.P. (2009) Synthesis and assembly of a full length human monoclonal antibody in algal chloroplast. Biotechnology and Bioengineering 104:663-673.
Muto, M., Henry, R., Mayfield (2009) Accumulation and processing of a recombinant protein designed as a cleavable fusion to the endogenous Rubisco LSU protein in Chlamydomonas chloroplast. BMC Biotechnology 9:26.
Beligni, M., Mayfield, S.P. (2008) Two ribosome-associated endoribonucleases, CSP41a and CSP41b, participate in chloroplast 23S ribosomal RNA maturation. Plant Mol. Bio. 67:389-401.
Merchant et al. (2007) The Chlamydomonas genome reveals the evolution of key animal and plant functions. Science 318:245-250.
Manuell, A.l., Quispe, J., Mayfield, S.P. (2007) Structure of the chloroplast ribosome: novel domains for translation regulation. PLoS Biol. 8: e209.
Mar�n-Navarro, J., Manuell, A.L, Wu, J., Mayfield, S.P. (2007) Chloroplast translation regulation. Photosynthesis 94:359-374.
Manuell, A., Beligni, M., Elder, J.H., Siefker, D., Tran, T., Weber, A., McDonald, T.L., Mayfield, S.P. (2007) Robust expression of a bioactive mammalian protein in Chlamydomonas chloroplast. Plant Biotech. J. 5:402-412.
Barnes, D., Franklin, S., Schultz, J., Henry, R., Brown, E., Coragliotti, A., Mayfield, S.P. (2006) Contribution of 5� and 3� untranslated regions in the expression of Chlamydomonas reinhardtii chloroplast genes. Molec. Genet. and Genom. 18:1-12.
Manuell, A., Yamaguchi, K., Haynes, P., Milligan, R., Mayfield, S.P. (2005) The composition and structure of 80S ribosome from the green alga Chlamydomonas reinhardtii: 80S ribosomes are conserved in plants and animals. J. Mol. Biol. 351:266-279.
Stephen Mayfield obtained bachelor of science degrees in Biochemistry and in Plant Biology from California Polytechnic University in San Luis Obispo in 1979, and a Ph.D. in Molecular Genetics from the University of California at Berkeley in 1984. From 1984 to 1987 Steve was an NIH post-doctoral fellow at the University of Geneva, Switzerland. In 1987 he joined the Scripps Research Institute and become a professor and associate dean of the graduate school before leaving to join UCSD in 2009.