Advances and perspectives of biosynthesis of chemicals based on CO2 and other one-carbon feedstocks

Abstract

Global warming and climate change, mainly caused by the emission of carbon dioxide, is becoming a serious problem, and it is imperative to develop efficient capture and utilization technologies for carbon dioxide and its derivatives one-carbon (C1) compounds. The use of CO2 and other C1 compounds, such as formate, methanol and formaldehyde, for biomanufacturing of industrial chemicals is of great importance in the transition from a fossil-dependent economy to a green and sustainable bioeconomy. This review article mainly focuses on the biosynthesis of chemicals with the use of C1 compounds in the context of synthetic biology and discusses the challenges as well as potential solutions in this field. First, we briefly highlight the development of synthetic biology and its relation to biomanufacturing as well as the introduction of low-carbon biosynthesis concept, which includes low-carbon feedstocks, low-carbon bioproduction process and low-carbon industrial chain. With a focus on C1 feedstocks, we then summarize the latest research advances in enhancing the carbon fixation efficiency of autotrophic microorganisms, empowering heterotrophs such as Escherichia coli and yeast with carbon fixation capabilities, and assembling cell-free machineries in biomanufacturing. Furthermore, we present a comparison of 10 natural and artificial CO2-fixation pathways, including their energy requirements and enzyme numbers in the corresponding pathway, which highlights the unique advantages of our recently developed integrated chemoenzymatic CO2 to amino-acid pathway (ICE-CAP) to turn CO2 into amino acids in a system without requirements for ATP/NAD(P)H and in only several steps. In the second part, we discuss the challenges faced in the chemical biosynthesis using C1 substrates, including the demand of high amounts of energy and reducing powers in carbon fixation pathways, low efficiency, low thermodynamic and kinetic driving forces of the pathway and the large gap between the practical needs of industrial applications and the currently limited capacity to use C1 compounds. As a promising solution, we presented the strategy to capture low-energy CO2 using the high-energy C1 compound methanol or formaldehyde in ICE-CAP to increase the energy utilization efficiencies. Furthermore, the low thermodynamic driving force in carbon-fixation pathways can be overcome by combining biocompatible chemistry (non-enzymatic) with enzymatic transformations. From the perspective of industrial applications, we illustrate the feasibilities of performing mixotrophic fermentation to enhancing the key parameters in terms of titer, yield and productivity in C1 utilization process for producing chemicals. Furthermore, we pay special attention to the key intermediate formaldehyde, which as an energy-intensive C1 synthon is of high interest for biosynthesis, in C1 fixation and emphasize its pivotal role in the conversion of inorganic carbon to organic carbon and carbon-chain elongation. Different pathways and routes are summarized that involve formaldehyde as an intermediate or a starting point for biosynthesis. The toxicity of formaldehyde in principle can be overcome through adaptive laboratory evolution, enzyme engineering, compartmentalization of formaldehyde utilization and other means. Formaldehyde can be readily produced from methanol, formate, CO and CO2. As one of the power sources in producing formaldehyde, we introduce a concept of bioelectrochemically converting biogas (CO2 and CH4) into formaldehyde. In the third part, we take 1,3-propanediol (PDO) as an example to illustrate our efforts to produce this important chemical from C1 compounds. Finally, we discuss the need and challenges to move from the proof of concept (“0 to 1”) in fundamental research to the industrial application (“1 to 100”), as well as the key scientific and technical issues for future development.