Biosystem design of Corynebacterium glutamicum for bioproduction.

Corynebacterium glutamicum, a natural glutamate-producing bacterium adopted for industrial production of amino acids, has been extensively explored recently for high-level biosynthesis of amino acid derivatives, bulk chemicals such as organic acids and short-chain alcohols, aromatics, and natural products, including polyphenols and terpenoids. Here, we review the recent advances with a focus on biosystem design principles, metabolic characterization and modeling, omics analysis, utilization of nonmodel feedstock, emerging CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) tools for Corynebacterium strain engineering, biosensors, and novel strains of C. glutamicum.

Utilization of microbial cocultures for converting mixed substrates to valuable bioproducts.

Utilization of microbial cocultures has been found to be a powerful approach for biochemical production. Cultivation of microbial co-culturescocultures on mixed substrates provides new opportunities and flexibility to control the growth and biosynthesis behavior of coculture members, and thus adds a new dimension for microbial coculture engineering. More generally, recruitment of microbial cocultures allows for efficient utilization of substrates to produce complex end products, which is challenging to achieve by monoculture approaches, which has been the traditional microbial engineering approach.

Harnessing electrical-to-biochemical conversion for microbial synthesis.

Electrical-to-biochemical conversion (E2BC) drives cell metabolism for biosynthesis and has become a promising way to realize green biomanufacturing. This review discusses the following aspects: 1. the natural E2BC processes and their underlying E2BC mechanism; 2.

Mitigation of host cell mutations and regime shift during microbial fermentation: a perspective from flux memory.

Microbial engineering forces flux redistribution to accommodate higher production rates, straining the cellular supply chain and leading to growth deficiency. Thus, there is a selective pressure to alleviate metabolic burden and revert towards the innate flux distribution ('flux memory') via mutations. Suboptimal fermentation exacerbates this phenomenon as increased number of generations prolong the selection window for the underlying flux memory to generate faster growing non-producers.

Making brilliant colors by microorganisms.

Anthocyanins, the colorful molecules found in plants, have positive health effects in humans, and are used as food colorants and nutraceuticals. Currently, the industrial supply of anthocyanins largely depends on extraction from plants, a method that lacks robustness and is potentially unsustainable. A promising alternative is biosynthesis by metabolically engineered microbes, which has achieved considerable success.

Advances in the development and application of microbial consortia for metabolic engineering.

Recent advances in metabolic engineering enable the production of high-value chemicals via expressing complex biosynthetic pathways in a single microbial host. However, many engineered strains suffer from poor product yields due to redox imbalance and excess metabolic burden, and require compartmentalization of the pathway for optimal function. To address this problem, significant developments have been made towards co-cultivation of more than one engineered microbial strains to distribute metabolic burden between the co-cultivation partners and improve the product yield.

Recent advances in modular co-culture engineering for synthesis of natural products.

The microbial production of natural products has been traditionally accomplished in a single organism engineered to accommodate target biosynthetic pathways. Often times, such approaches result in large metabolic burdens as key cofactors, precursor metabolites and energy are channeled to pathways of structurally complex chemicals. Recently, modular co-culture engineering has emerged as a new approach to efficiently conduct heterologous biosynthesis and greatly enhance the production of natural products.

The road to animal-free glycosaminoglycan production: current efforts and bottlenecks.

Animal-extraction, despite its limitations, continues to monopolize the fast-growing glycosaminoglycan (GAG) industry. The past few years have seen an increased interest in the development of alternative GAG production methods. Chemical and chemo-enzymatic synthesis and biosynthesis from GAG producing cells, including engineered recombinant strains, are currently under investigation.

Microbial production of value-added nutraceuticals.

Nutraceuticals are important natural bioactive compounds that confer health-promoting and medical benefits to humans. Globally growing demands for value-added nutraceuticals for prevention and treatment of human diseases have rendered nutraceuticals a multi-billion dollar market. However, supply limitations and extraction difficulties from natural sources such as plants, animals or fungi, restrict the large-scale use of nutraceuticals.

Sensitive cells: enabling tools for static and dynamic control of microbial metabolic pathways.

Natural metabolic pathways are dynamically regulated at the transcriptional, translational, and protein levels. Despite this, traditional pathway engineering has relied on static control strategies to engender changes in metabolism, most likely due to ease of implementation and perceived predictability of design outcome. Increasingly in recent years, however, metabolic engineers have drawn inspiration from natural systems and have begun to harness dynamically controlled regulatory machinery to improve design of engineered microorganisms for production of specialty and commodity chemicals.