Corynebacterium glutamicum, Escherichia coli, and Saccharomyces cerevisiae in particular, have become established as important industrial workhorses in biotechnology. Recent years have seen ...tremendous progress in their advance into tailor‐made producers, driven by the upcoming demand for sustainable processes and renewable raw materials. Here, the diversity and complexity of nature is simultaneously a challenge and a benefit. Harnessing biodiversity in the right manner through synergistic progress in systems metabolic engineering and chemical synthesis promises a future innovative bio‐economy.
From cells to cell factories: Modern biotechnology combines systems metabolic and genetic engineering to enable microbes to produce natural value‐added products. The picture illustrates the upgrade of the complex cellular metabolism into an industrial cell factory.
Highlights ► C. glutamicum as production platform for a rich bio-based product portfolio. ► Systems metabolic engineering of C. glutamicum is driving industrial strain optimization. ► Synthetic cell ...factories can compete with classical production strains from 50 years of optimization. ► Exploitation of non-food feedstocks is gaining importance for sustainable production. ► Synthetic metabolic engineering extends applications to artificial pathways and non-natural chemicals.
Pseudomonas putida
is a Gram-negative, rod-shaped bacterium that can be encountered in diverse ecological habitats. This ubiquity is traced to its remarkably versatile metabolism, adapted to ...withstand physicochemical stress, and the capacity to thrive in harsh environments. Owing to these characteristics, there is a growing interest in this microbe for industrial use, and the corresponding research has made rapid progress in recent years. Hereby, strong drivers are the exploitation of cheap renewable feedstocks and waste streams to produce value-added chemicals and the steady progress in genetic strain engineering and systems biology understanding of this bacterium. Here, we summarize the recent advances and prospects in genetic engineering, systems and synthetic biology, and applications of
P. putida
as a cell factory.
Key points
• Pseudomonas putida advances to a global industrial cell factory.
• Novel tools enable system-wide understanding and streamlined genomic engineering.
• Applications of P. putida range from bioeconomy chemicals to biosynthetic drugs.
Corynebacterium glutamicum is a major workhorse in industrial biotechnology. For the past several decades, this soil bacterium has been used to produce the amino acids l-glutamate and l-lysine at a ...level of 6 million tons per year. Utilizing novel genome editing methods and advanced tools of systems and synthetic biology, the portfolio of C. glutamicum has exploded from classical food and feed products to the chemical industry, cosmetics and healthcare applications. Within the past five years, the number of industrial products has almost doubled to approximately 70 natural and non-natural compounds. This review summarizes the state-of-the-art regarding metabolically engineered cell factories of C. glutamicum, illustrates recent key technological developments and provides examples of the major industrial applications of this important microbe.
•Genome-editing of the microbe allows for multiplexed genomic engineering.•Biosensors display a key innovation to drive strain development and screening.•Metabolically engineered Corynebacterium glutamicum is meanwhile applied to produce more than 70 products.•Novel substrate assimilation routes strongly expand the raw material basis for renewable bio-production.
Fluxome analysis using GC-MS Wittmann, Christoph
Microbial cell factories,
02/2007, Letnik:
6, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Fluxome analysis aims at the quantitative analysis of in vivo carbon fluxes in metabolic networks, i. e. intracellular activities of enzymes and pathways. It allows investigating the effects of ...genetic or environmental modifications and thus precisely provides a global perspective on the integrated genetic and metabolic regulation within the intact metabolic network. The experimental and computational approaches developed in this area have revealed fascinating insights into metabolic properties of various biological systems. Most of the comprehensive approaches for metabolic flux studies today involve isotopic tracer studies and GC-MS for measurement of the labeling pattern of metabolites. Initially developed and applied mainly in the field of biomedicine these GC-MS based metabolic flux approaches have been substantially extended and optimized during recent years and today display a key technology in metabolic physiology and biotechnology.
In the rising era of bio-economy, the five carbon compound 1,5-diaminopentane receives increasing interest as platform chemical, especially as innovative building block for bio-based polymers. The ...vital interest in bio-based supply of 1,5-diaminopentane has strongly stimulated research on the development of engineered producer strains. Based on the state-of-art knowledge on the pathways and reactions linked to microbial 1,5-diaminopentane metabolism, the review covers novel systems metabolic engineering approaches towards hyper-producing cell factories of
Corynebacterium glutamicum
or
Escherichia coli
. This is integrated into the whole value chain from renewable feedstocks via 1,5-diaminopentane to innovative biopolymers involving bioprocess engineering considerations for economic supply.
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•PUFAs are applied worldwide in superfoods, aquafeed and pharmaceuticals.•Climate warming and declining fishery cause a severe supply and demand gap.•The PUFAs EPA and DHA are most ...impactful and offer lucrative opportunities.•The best PUFA cell factories are derived from microalgae, yeasts, and fungi.•Metabolic engineering creates a next level of production performance.
Polyunsaturated fatty acids (PUFAs), primarily docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), have received worldwide attention in recent years due to an increasing awareness of their uniqueness in improving diet and human health and their apparently inevitable shortage in global availability. Microbial cell factories are a major solution to supplying these precious molecules in sufficient amounts and providing PUFA-rich aquafeed, superfoods, and medical formulations. This review assesses the PUFA world markets and highlights recent advances in upgrading and streamlining microalgae, yeasts, fungi, and bacteria for high-level PUFA production and broadening of the PUFA spectrum.
Industrial Biotechnology Christoph Wittmann, James C. Liao / Sang Yup Lee, Jens Nielsen, Gregory Stephanopoulos / Christoph Wittmann, James C. Liao
2016, 2017, 2016-11-23, 2016-11-18, 20170306
eBook
The latest volume in the Advanced Biotechnology series provides an overview of the main product classes and platform chemicals produced by biotechnological processes today, with applications in the ...food, healthcare and fine chemical industries. Alongside the production of drugs and flavors as well as amino acids, bio-based monomers and polymers and biofuels, basic insights are also given as to the biotechnological processes yielding such products and how large-scale production may be enabled and improved. Of interest to biotechnologists, bio and chemical engineers, as well as those working in the biotechnological, chemical, and food industries.
Cis, cis-muconic acid (MA) is a dicarboxylic acid of recognized industrial value. It provides direct access to adipic acid and terephthalic acid, prominent monomers of commercial plastics.
In the ...present work, we engineered the soil bacterium Corynebacterium glutamicum into a stable genome-based cell factory for high-level production of bio-based MA from aromatics and lignin hydrolysates. The elimination of muconate cycloisomerase (catB) in the catechol branch of the β-ketoadipate pathway provided a mutant, which accumulated MA at 100% molar yield from catechol, phenol, and benzoic acid, using glucose as additional growth substrate. The production of MA was optimized by constitutive overexpression of catA, which increased the activity of the encoded catechol 1,2-dioxygenase, forming MA from catechol, tenfold. Intracellular levels of catechol were more than 30-fold lower than extracellular levels, minimizing toxicity, but still saturating the high affinity CatA enzyme. In a fed-batch process, the created strain C. glutamicum MA-2 accumulated 85 g L
MA from catechol in 60 h and achieved a maximum volumetric productivity of 2.4 g L
h
. The strain was furthermore used to demonstrate the production of MA from lignin in a cascade process. Following hydrothermal depolymerization of softwood lignin into small aromatics, the MA-2 strain accumulated 1.8 g L
MA from the obtained hydrolysate.
Our findings open the door to valorize lignin, the second most abundant polymer on earth, by metabolically engineered C. glutamicum for industrial production of MA and potentially other chemicals.
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