a bistable gene switch for antibiotic biosynthesis the butyrolactone regulon in streptomyces coelicolor抗生素生物合成的基因双稳态开关丁内酯调节子在链霉菌属coelicolor.pdfVIP

A Bistable Gene Switch for Antibiotic Biosynthesis: The Butyrolactone Regulon in Streptomyces coelicolor 1 2 3 2 Sarika Mehra , Salim Charaniya , Eriko Takano , Wei-Shou Hu * 1 Department of Chemical Engineering, Indian Institute of Technology Bombay, Powai, Mumbai, India, 2 Department of Chemical Engineering and Materials Science, University of Minnesota, Minneapolis, Minnesota, United States of America, 3 Department of Microbiology, University of Groningen, Groningen, The Netherlands Abstract Many microorganisms, including bacteria of the class Streptomycetes, produce various secondary metabolites including antibiotics to gain a competitive advantage in their natural habitat. The production of these compounds is highly coordinated in a population to expedite accumulation to an effective concentration. Furthermore, as antibiotics are often toxic even to their producers, a coordinated production allows microbes to first arm themselves with a defense mechanism to resist their own antibiotics before production commences. One possible mechanism of coordination among individuals is through the production of signaling molecules. The c-butyrolactone system in Streptomyces coelicolor is a model of such a signaling system for secondary metabolite production. The accumulation of these signaling molecules triggers antibiotic production in the population. A pair of repressor-amplifier proteins encoded by scbA and scbR mediates the production and action of one particular c-butyrolactone, SCB1. Based on the proposed interactions of scbA and scbR, a mathematical model was constructed and used to explore the ability of this system to act as a robust genetic switch. Stability analysis shows that the butyrolactone system exhibits bistability and, in re