Chen, ZhenZhenChenZeng, An-PingAn-PingZeng2020-07-162020-07-162013-04-16Biotechnology Journal 5 (8): 523-533 (2013)http://hdl.handle.net/11420/6860Accelerating the process of industrial bacterial host strain development, aimed at increasing productivity, generating new bio-products or utilizing alternative feedstocks, requires the integration of complementary approaches to manipulate cellular metabolism and regulatory networks. Systems metabolic engineering extends the concept of classical metabolic engineering to the systems level by incorporating the techniques used in systems biology and synthetic biology, and offers a framework for the development of the next generation of industrial strains. As one of the most useful tools of systems metabolic engineering, protein design allows us to design and optimize cellular metabolism at a molecular level. Here, we review the current strategies of protein design for engineering cellular synthetic pathways, metabolic control systems and signaling pathways, and highlight the challenges of this subfield within the context of systems metabolic engineering. Within the context of systems metabolic engineering, protein design can be utilized to introduce new enzyme function or substrate spectrum for the construction of novel synthetic pathways. This review discusses tools such as improving enzyme properties for the optimization of pathway efficiency, altering the specificity of transcription regulators or allosteric proteins to rewire regulation network, or building protein scaffolds for metabolite channeling or altering signaling transduction pathways - all of which could be combined to accelerate the process of industrial strain development. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.en1860-731420135523533Wiley-VCHDynamic flux controlProtein designScaffold proteinSynthetic pathwaySystems metabolic engineeringBiowissenschaften, BiologieJournal Article10.1002/biot.201200238Other