Sustainable production of chemicals from renewable non-food biomass has become a promising alternative to overcome environmental issues caused by our heavy dependence on fossil resources. Systems metabolic engineering, which integrates traditional metabolic engineering with systems biology, synthetic biology, and evolutionary engineering, is enabling the development of microbial cell factories capable of efficiently producing a myriad of chemicals and materials including biofuels, bulk and fine chemicals, polymers, amino acids, natural products and drugs. In this paper, many tools and strategies of systems metabolic engineering, including in silico genome-scale metabolic simulation, sophisticated enzyme engineering, optimal gene expression modulation, in vivo biosensors, de novo pathway design, and genomic engineering, employed for developing microbial cell factories are reviewed. Also, detailed procedures of systems metabolic engineering used to develop microbial strains producing chemicals and materials are showcased. Finally, future challenges and perspectives in further advancing systems metabolic engineering and establishing biorefineries are discussed.

中文翻译：

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用于开发用于化学生产的微生物细胞工厂的系统代谢工程学的工具和策略。

由可再生的非食品生物质可持续生产化学物质已成为解决我们严重依赖化石资源所引起的环境问题的有前途的替代方法。系统代谢工程学将传统的代谢工程学与系统生物学，合成生物学和进化工程学相结合，使微生物细胞工厂的发展成为可能，这些工厂能够有效生产多种化学物质和材料，包括生物燃料，散装和精细化学物质，聚合物，氨基酸，天然产物和药物。本文介绍了系统代谢工程的许多工具和策略，包括计算机模拟基因组规模的代谢模拟，复杂的酶工程，最佳基因表达调控，体内生物传感器，审查了用于发展微生物细胞工厂的从头途径设计和基因组工程。此外，还展示了用于开发可产生化学物质和材料的微生物菌株的系统代谢工程学的详细程序。最后，讨论了进一步推进系统代谢工程和建立生物精炼厂的未来挑战和前景。