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Metabolic engineering of complex biomolecules

This research investigates microbial cells as biological synthesis platforms to generate novel, synthetic chemicals as well as to overproduce naturally occurring biomolecules.

Chimeric cellulose - Cellulose is the most abundant polymer on earth, yet is underutilized as a biomaterial, particularly for biomedical applications, due to: lack of degradability, difficultly in purification (from plant sources) and further processing, and limitations in surface functionalization. We explore the metabolic engineering of a novel bacterial system (Acetobacter xylinum) that is able to synthesize and processes cellulose chains directly into membrane mats by extrusion of the pure polymer through membrane pores into crystallized matrices. Our approach exploits this unusual coupled biosynthesis-processing system to incorporate a broader suite of carbohydrate chemistries directly into the polymer chains.  The focus is on redesigning the native metabolism of this unique microbe to integrate heterologous pathways for nitrogen-containing sugars. We address two major design and implementation level challenges. One major hurdle is to ensure that integrating the heterologous pathway elements does not disrupt growth or otherwise compromise normal cellular function. Indeed, the synthetic goal may directly compete with the native objective of the cell, because natural systems have evolved to optimize growth and survival, rather than the formation of a single metabolite or biosynthetic product. The second, technical hurdle involves the genetic manipulation of a novel, niche microbial production host.



  • Yadav V, Panilaitis B, Shi H, Lee K, Cebe P, et al. (2010) A novel in vivo-degradable cellulose-chitin copolymer from metabolically engineered Gluconacetobacter xylinus. Appl Environ Microbiol in press.