I enjoyed reading Charlotte Hsu's article "Engineers turn E. coli into tiny factories for producing new forms of popular antibiotic," which describes the accomplishment of UB scientists in combatting antibiotic resistance by genetically modifying and metabolically engineering E. coli bacteria to produce variations of the antibiotic erythromycin. Their feat marks another triumph for the relatively new science of synthetic biology — the application of engineering techniques to biology in order to produce new life forms useful for solving global health and environmental problems, and for advancing the scientific understanding of life itself.

As noted in the article, Dr. Pfeifer and colleagues have been pursuing this goal for more than a decade. Their persistent hard work is revealed in the following milestones found in a PubMed search of journal articles:

• March 2001, Microbiology and Molecular Biology Reviews. The bacterium that naturally produces erythromycin is difficult to work with. More "genetically amenable microbes" like E. coli were developed as heterologous (different species) hosts for production of erythromycin.
• November 2003, Applied and Environmental Microbiology. Reported the successful biosynthesis of the compound yersiniabactin in E. coli. This success will aid in the future production of similar compounds like erythromycin.
• January 2008, Metabolic Engineering. "Chromosomal engineering" was used to place in E. coli the genes required for production of the compound known as 6dEB, "a precursor to the antibiotic erythromycin."
• May 2009, Microbial Biotechnology. The exploration and adjustment of "gene dosage levels" in the metabolic pathways responsible for production of the erythromycin precursor 6dEB in E. coli.
• April 2010, BMC Systems Biology. Described a "genetic algorithm and elementary mode analysis" to find metabolic pathways for production of the "industrially relevant products" ethanol and lycopene. This same system can be applied toward the production of any desired product.
• November 2010, Chemistry & Biology. Erythromycin is naturally produced by the bacterium Saccharopolyspora erythraea. In this study, the genes to produce erythromycin were transferred to E. coli bacteria and the metabolic pathways were modified to produce two variations or "analogs" of erythromycin.
• June 2011, Biotechnology and Bioengineering. The authors "over-express three different pathways" for production of erythromycin in E. coli in order to develop possible variations of erythromycin.
• January 2012, Biotechnology Progress. Production of erythromycin in several variations of metabolically engineered E. coli was compared.
• January 2013, Journal of Visualized Experiments. "The Logic, Experimental Steps, and Potential" for production of erythromycin in E. coli was described. The goal was to "set the stage for future engineering efforts to improve or diversify production."
• July 2013, Biotechnology Progress. The authors reduced the total number of genes transferred to E. coli to streamline and stabilize the metabolic process. This led to increased volume of erythromycin production and also suggested other possible changes for metabolic pathway engineering.
• September 2013, Metabolic Engineering. Production of erythromycin in E. coli requires not only the transfer of 19 foreign genes, but also the engineering of E. coli metabolic pathways to produce compounds necessary for erythromycin formation. This study compared three possible pathways.
• November 2013, Metabolic Engineering. Two metabolic pathways in E. coli were interchanged in order to produce new forms of erythromycin. Two new forms were produced, both "exhibited bioactivity" against antibiotic resistant bacter
• June 2014, Current Opinion in Plant Biology. Summarizes success achieved thus far using the tools of metabolic engineering and synthetic biology to produce desired compounds such as the anti-malaria drug artemisinin in E. coli and other heterologous hosts.

Hsu's article led me to read the research article she reported on: "Tailoring pathway modularity in the biosynthesis of erythromycin analogs heterologously" by UB scientists Guojian Zhang, Yi Li, Lei Fang and Blaine A. Pfeifer. They note that their success helps to clarify the scientific understanding of the mechanisms involved in producing complex metabolic products such as erythromycin within the cell. They conclude that their research will provide "additional metabolic engineering and synthetic biology tools? to other scientists in their efforts to provide useful products and to understand cellular mechanisms.

Thank you UB Reporter and Charlotte Hsu for informing us of the masterful achievement attained by scientists in UB's Department of Chemical and Biological Engineering!

William Dale, UB EdM, Science and the Public Program,

Graduate School of Education