The trends towards using green chemical and energy are increasing due to the growing demand for non-fossil bio-products, the environmental concern for using fossil fuel, and the continuously increasing cost of crude oils. The total annual markets of biofuels and biochemicals are estimated to exceed $1 trillion [1]. Microbial fermentation has been widely used to produce organic biochemicals and biofuels, including citric acid, lactic acid, butyric acid, propionic acid, amino acids, ethanol, propanol, butanol, etc. The rapidly growing biotechnology market requires an efficient bioprocess platform, including both the production cell and the process, for biochemicals and biofuels production. Metabolic engineering (ME) is often used to develop high-producing cells needed for the process. However, ME requires genetically modifying the cell, which can be difficult to do or

to achieve the expected outcome, especially for less studied microorganisms. Metabolic process engineering (MPE) is a novel and advanced technology that alters or manipulates metabolic pathway to produce the interested metabolites by rationally controlling or manipulating bio-production process parameters. The goal of MPE is to achieve a high-productivity, high-quality, robust and scalable process through dynamic monitoring and investigating the interactions between cellular metabolism and process parameters. Different from the well-known traditional fermentation process development, MPE targets to engineer the bio-production process by controlling the cell physiology and metabolic responses to changes in fermentation process parameters and incorporating the interplay between cell and process into the rational process design. In this article, we focus on the application of MPE to improve biochemicals and biofuels production via precise bioreactor controllers, in situ sensors, and omics technologies.