Table of Contents
Journal of Synthetic Biology
Volume 2015 (2015), Article ID 178514, 10 pages
http://dx.doi.org/10.1155/2015/178514
Research Article

Synthetic Crossfeeding Cocultures in Yeast: Computational Model of Autoregulation and Design of a Tryptophan Export Device

1Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Intendente Güiraldes 2160, Ciudad Universitaria, 1428 Buenos Aires, Argentina
2Departamento de Fisiología, Biología Molecular y Celular, Instituto de Fisiologia, Biologia Molecular y Neurociencias, Consejo Nacional de Investigaciones Científicas y Técnicas and Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Intendente Güiraldes 2160, Ciudad Universitaria, 1428 Buenos Aires, Argentina
3Departamento de Computación, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Intendente Güiraldes 2160, Ciudad Universitaria, 1428 Buenos Aires, Argentina
4Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires and IQUIBICEN-CONICET, Intendente Güiraldes 2160, Ciudad Universitaria, 1428 Buenos Aires, Argentina
5Protein Physiology Laboratory, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires and IQUIBICEN-CONICET, Intendente Güiraldes 2160, Ciudad Universitaria, 1428 Buenos Aires, Argentina

Received 14 August 2014; Revised 16 January 2015; Accepted 20 January 2015

Academic Editor: Andres Moya

Copyright © 2015 Alan Bush et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

In order to contribute to the design of crossfeeding systems, we modeled population control in a coculture of two crossfeeding strains of an organism, each of which secretes a metabolite the other strain requires to grow. Differential equations show that the steady-state population ratio can be tuned by varying the ratio of the metabolite secretion rates, as long as they fall within a range determined by the nature of the organism. Numerical simulations of Trp/His crossfeeding in budding yeast suggest that the time required to reach steady state populations critically depends on the capacity of the cells to uptake the crossfeeding amino acids. We also engineered and evaluated a novel genetic device that secretes tryptophan-rich peptides with a cell penetrating sequence. Experimental validation showed that the device increases tryptophan secretion and enables growth of a trp strain in a coculture in synthetic medium lacking tryptophan.