Systems and Synthetic Biology Advances for Engineering Non-Model Microorganisms

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Background

With mounting concerns over climate change, excessive carbon emissions, and impending fossil resource scarcity, the world is actively researching for greener bio-based alternatives to synthesize a myriad of chemicals with broad applications in our modern society. Model organisms like Escherichia coli and Saccharomyces cerevisiae have long served as microbial workhorses to produce renewable chemicals due to our extensive knowledge of their physiology and availability of systems and synthetic biology tools. However, they are not necessarily the best-suited systems for all bioproducts and applications. With the continual decrease in the cost for genome sequencing, it has become feasible to explore a wider range of microbes that are largely understudied but have the potential to be extremely efficient microbial cell factories. Non-conventional microbes possess the ability to naturally utilize a wide range of substrates, produce complex molecules, and function at a wide range of temperature and pH and therefore, have been gaining attention in recent years as cell factories. However, the limited knowledge on their cultivation conditions, integrative omics, and synthetic biology tools have hampered their widespread implementation as microbial cell factories. The unprecedented rapid research and development in the fields of systems and synthetic biology in recent years have contributed to elucidate and engineer non-model hosts for the optimal synthesis of desired fuels and chemicals. Fortunately, this field is steadily gaining attention and will be an important research topic in the years to come.

Non-model organisms are proposed to be better suited for large-scale production of specific chemicals and biofuels compared to model organisms due to properties like tolerance to extreme conditions, assimilation of diverse carbon sources, and diversity of enzymes and metabolic pathways. This endeavor can be assisted by the emerging fields of systems and synthetic biology towards metabolic engineering of potential hosts. The recent advances in the development of mathematical models for non-model microbes to reconstruct their cellular metabolisms can accelerate the systems-level understanding and optimization of metabolic pathways and help with the identification of new potential target compounds. Additionally, synthetic biology has made CRISPR/Cas9 based toolkits and novel genetic regulatory parts available for many non-model organisms, which will assist in rapid and precise genetic modifications. Using both systems and synthetic biology, it will be possible to
modify organisms into cell factories for conversion of cheap and sustainable feedstocks into valuable molecules, thus forwarding a bio-based economy. The goal of this Research Topic is to compile and provide a platform to discuss recent breakthroughs related to the discovery, development, and implementation of the aforementioned technologies for metabolic engineering of non-model organisms.

This Research Topic is particularly interested in articles demonstrating and discussing computational methods for the design of non-model microbial cell factories, as well as novel experimental approaches for the design and application of new genetic circuits, gene products, and other integrative approaches for understanding and manipulating their metabolic pathways.
We are interested in both original research articles and reviews on the following subjects:
· Computational and/or experimental approaches for engineering novel non-model genetic systems
· Integrative approaches on genetic circuit design and their principles of organization into programs
· Creation, analysis and applications of genetic parts libraries
· Experimental quantification of metabolic fluxes
· Metabolic engineering for the production of novel fuel molecules and chemicals
· Natural products discovery and homologous or heterologous enzyme expression to promote microbial synthesis
· Innovative cellular programming approaches for deconstruction and conversion of complex substrates including carbon dioxide, methane and methanol
· Development of genome editing tools, particularly those based on the CRISPR/Cas systems, for non-model microorganisms
· Construction of optimization of genetic parts and circuits for non-model microorganisms
· Reconstruction and analysis of genome-scale metabolic model of non-model organism
· Metagenomics and applications of synthetic metagenome

Keywords: cellular reprogramming, genome-scale metabolic models, genetic toolkits, synthetic gene circuits, metagenomics, genome editing, microbial cell factories

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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