Cooperative Co-culture of Escherichia coli and Saccharomyces cerevisiae for Overproduction of Paclitaxel Precursors

Kang Zhou 1, Kangjian Qiao 1, Steven Edgar 1, Gregory Stephanopoulos 1, *

Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, the USA1

* To whom correspondence should be addressed. E-mail: gregstep@mit.edu

Abstract

In nature, there are many examples of microbial consortia that can efficiently accomplish chemically difficult processes through the division of labor among different species. To date, such strategy has not been fully explored in engineering microbes for production of valuable metabolites. In this study, we demonstrated a synthetic cooperative microbial system to produce precursors of anti-cancer drug paclitaxel by using two model laboratory microbes, E. coli and S. cerevisiae. The two species with distinct advantages cooperated synergistically in two levels, cell growth and taxane production. This design could also make the engineering of paclitaxel biosynthetic pathway to be more modular, because each species carrying part of the pathway can be optimized individually and then simply mixed together to complete the whole pathway. Because of these advantages, the concept demonstrated in this project, cooperation of multiple cells with their own specialties, should be generally applicable to many other similar processes.