design constraints on a synthetic metabolism合成代谢设计约束.pdfVIP

Design Constraints on a Synthetic Metabolism Tugce Bilgin1,2*, Andreas Wagner1,2,3 ¨ 1 Institute of Evolutionary Biology and Environmental Sciences, University of Zurich, Zurich, Switzerland, 2 The Swiss Institute of Bioinformatics, Zurich, Switzerland, 3 The Santa Fe Institute, Santa Fe, New Mexico, United States of America Abstract A metabolism is a complex network of chemical reactions that converts sources of energy and chemical elements into biomass and other molecules. To design a metabolism from scratch and to implement it in a synthetic genome is almost within technological reach. Ideally, a synthetic metabolism should be able to synthesize a desired spectrum of molecules at a high rate, from multiple different nutrients, while using few chemical reactions, and producing little or no waste. Not all of these properties are achievable simultaneously. We here use a recently developed technique to create random metabolic networks with pre-specified properties to quantify trade-offs between these and other properties. We find that for every additional molecule to be synthesized a network needs on average three additional reactions. For every additional carbon source to be utilized, it needs on average two additional reactions. Networks able to synthesize 20 biomass molecules from each of 20 alternative sole carbon sources need to have at least 260 reactions. This number increases to 518 reactions for networks that can synthesize more than 60 molecules from each of 80 carbon sources. The maximally achievable rate of biosynthesis decreases by approximately 5 percent for every additional molecule to be synthesized. Biochemically related molecules can be synthesized