Growth Strategies of Microbes on mixed carbon Sources

A classic problem in microbiology is that bacteria display two types of growth behavior when cultured on a mixture of two carbon sources: in certain mixtures the bacteria consume the two carbon sources sequentially (diauxie) and in other mixtures the bacteria consume both sources simultaneously (co-utilization). The search for the molecular mechanism of diauxie led to the discovery of the lac operon and gene regulation in general. However, questions remain as why microbes would bother to have different strategies of taking up nutrients and in the case of co-utilization what determines the partition and distribution of carbon sources in the cell. Here we show that diauxie versus co-utilization can be understood from the topological features of the metabolic network. A model of optimal allocation of protein resources quantitatively explains why and how the cell makes the choice when facing multiple carbon sources. When two carbon sources are being co-utilized, the model predicts the percentage of each carbon source in supplying the synthesis of every type of amino acid, which is quantitatively verified by experiments. Our work solves a long-standing puzzle and provides a quantitative framework for the carbon source utilization of microbes.