Harnessing Microbial Factories: Biotechnology at the Edge of Synthetic Chemistry

Abstract

The interplay of biotechnology and synthetic chemistry has brought a revolutionary age in the synthesis of complex chemicals, fuels and pharmaceuticals. Engineered microorganisms (also known as microbial factories) that can perform specific biochemical reactions have become a promising sustainable and highly versatile platform to synthesize high-value compounds that are frequently difficult to prepare in a conventional chemical synthetic pathway. In the present paper, we discuss the state-of-the-art approaches used in microbial engineering, such as genome editing, optimization of metabolic pathways, and the expression of synthetic regulatory circuits, to improve the efficiency, yield, and specificity of microbial biosynthesis. It focuses on the combination of systems biology and computational modeling to predict metabolic fluxes and inform rational strain design to reduce trial-and-error methods. Successful uses are discussed in case studies, e.g. the microbial synthesis of bioactive natural products, specialty chemicals and next-generation biofuels, and illustrate the ability of engineered microbes to fill in the gap between biology and synthetic chemistry. Also, the paper discusses the main issues, such as metabolic load, pathway crosstalk, and scalability, regulatory and biosafety implications of the implementation of microbial factories in the industrial environment. The emerging technologies, including artificial intelligence-based strain optimizations and cell-free synthetic platforms, which are discussed in the discussion, also have the potential to further expand the capabilities of microbial factories. This paper will illuminate both the scientific concepts and application of microbial biotechnology to give a thorough perspective of how microbial systems will be utilized in the form of modular and programmable chemical factories. These results point to the potential of microbial engineering as a device to produce chemicals sustainably as well as to generate novelty at the interface of biology, chemistry, and industrial biotechnology.