Recent progress in the metabolic engineering of alkaloids in plant systems

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Highlights► Recent metabolic engineering efforts for plant alkaloids. ► Characterizing, reconfiguring and fine-tuning metabolic ‘parts’ improves titers. ► Additional strategies are necessary to produce ‘unnatural’ natural products.     

Metabolic network flux analysis for engineering plant systems

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Highlights► A powerful range of tools has been developed for metabolic network flux analysis. ► These tools yield insights that are used to aid microbial metabolic engineering. ► Plants present great opportunities and special challenges to applying these tools. ► Tool selection and knowledge of plant systems is key to practical success.     

Comparative genomics approaches to understanding and manipulating plant metabolism

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Highlights► Comparative genomics can help predict the function of unknown plant metabolic genes. ► Functional gene annotations are foundational to the construction of metabolic models. ► Models can simulate effects of genetic changes and thus guide metabolic engineering. ► Examples of comparative genomics facilitating gene discovery in plants are presented.     

Transcriptome data modeling for targeted plant metabolic engineering

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Highlights► Network analysis is essential for data mining of omics-based large-scale data sets. ► Gene coexpression analysis is useful for prediction of gene function. ► Comparative network analysis can reveal common and unique plant metabolic pathways. ► Novel genome editing tools facilitate rational metabolic engineering.     

Enzyme and metabolic engineering for the production of novel biopolymers: crossover of biological and chemical processes

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Highlights► Poly(ω-hydroxy fatty acids) are polyethylene-like biobased polyester. ► Medium-chain-length polyhydroxyalkanoate homopolymers are processed to stretchy film. ► Microbial lactate-based polyesters exhibit transparent and flexible properties. ► Enzyme and metabolic engineering facilitates the expanding of bio-based polymers.     

The emerging field of transport engineering of plant specialized metabolites

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Highlights► Transport engineering has the potential to increase nutritional value of crops. ► Transport engineering can increase yield of synthetic biology approaches. ► Neo-functionalization of primary metabolite transporters to specialized metabolism. ► Elimination of glucosinolate seed accumulation is achieved via transport engineering. ► Glucosinolates in Arabidopsis: a model for transport of specialized metabolites.     

The interface between plant metabolic engineering and human health

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Highlights► People should increase their consumption of fruit and vegetables to reduce their risk of chronic diseases. ► Despite many campaigns uptake of fruit and vegetable consumption has been limited. ► Metabolic engineering can improve understanding of the roles of dietary phytonutrients. ► Data from nutritional studies of model foods can set targets for crop improvements. ► Nutritionally enhanced fruit and vegetables, developed through breeding or metabolic engineering, could contribute to health.     

From measurement to implementation of metabolic fluxes

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Highlights► In vivo flux distributions can be determined with increasing accuracy and breadth. ► Enzyme activity can partly be identified from codon usage and other DNA features. ► Stoichiometric constraints of metabolism set a frame that can be exploited to design efficient metabolic networks. ► Insights into DNA-sequence–function relationships lead to first examples of rational DNA writing. ► Increasing DNA synthesis speed moves metabolic engineering from tinkering to green field design.     

Stable isotope-assisted metabolomics to detect metabolic flux changes in mammalian cell cultures

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Highlights► Stable isotope-assisted metabolomics is powerful to determine metabolic fluxes. ► Stable isotope-assisted metabolomics is more complex for mammalian cell cultures. ► Biotechnological processes can be improved by assessing metabolic flux changes. ► Metabolic flux analysis is an attractive tool for toxicity studies. ► There is a huge potential for future applications on mammalian systems.     

Profiling metabolic networks to study cancer metabolism

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Highlights► Metabolic dependencies that arise in tumors may present new opportunities for therapy. ► Advanced methods in metabolic systems biology can help identify these dependencies. ► Application of isotope tracers to cancer models can facilitates quantitation of fluxes. ► Tumors with compromised TCA metabolism exhibit unique metabolic profiles.     

Metabolomics platforms for genome wide association studies—linking the genome to the metabolome

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Highlights► Genome-wide association studies with metabolomics constitute mGWAS. ► mGWAS provide insights into genetic and environmental impact on metabolic processes. ► We review essential strategies for mGWAS. ► Examples of mGWAS in large cohort studies are discussed.     

Alkylating enzymes

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Highlights► Alkylating enzymes allow regiospecific and chemospecific reactions where classical chemical syntheses fail or require an extensive protection strategy. ► Prenyltransferase and methyltransferase are increasingly applicable in biotechnology. ► Cofactor or cosubstrate availability can still be a limiting factor. ► Enzyme cascade reactions and/or whole-cell systems are applied to perform multiple step transformations. ► Alkyltransferases are crucial elements in pathway engineering and synthetic biology, especially toward plant derived (natural) products.     

Lipid metabolism in microalgae distinguishes itself

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Highlights► Triacylglycerol assembly in microalgae might occur at plastid envelopes. ► Starch-less mutants provide clues for the engineering of carbon partitioning in algae. ► New algal species emerge as models for lipid and biofuel research.     

Plant genome-scale metabolic reconstruction and modelling

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Highlights► Recent advances have been made on plant genome-scale metabolic reconstruction. ► Cellular compartmentation makes plant genome-scale reconstruction challenging. ► Current reconstructions capture important features of plant metabolism. ► The models have been used to study isolated tissues and tissue interaction. ► We review the challenges and potential of plant reconstruction and modelling.     

Network,nodes and nexus: systems approach to multitarget therapeutics

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Highlights► Complex diseases are an outcome of multiple triggers that precipitate into similar phenotypes. ► Systems level understanding can reveal dynamic aspects of disease progression profile. ► Correlation of metabolic remodeling to phenotypic alteration can delineate critical nodes of interventions. ► Multitargeting of key nodes of metabolic networks can be an effective therapeutic strategy. ► Robust and high-throughput data integration in conjunction with simulation would make the drug discovery process more efficient.     

Pathway and protein engineering approaches to produce novel and commodity small molecules

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Highlights► Production of novel pharmaceutical and commodity chemicals. ► Protein and pathway engineering pave the way for product diversifications. ► ‘Omics’ data have helped assembly of pathways from different species. ► Recombination of enzymatic domains and site-directed mutagenesis. ► Tunable control of pathways for better production.     

Engineering specialized metabolic pathways—is there a room for enzyme improvements?

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Highlights► Specialized metabolism offers challenging engineering opportunities. ► Unlike central metabolism, specialized metabolism is slow, sluggish and messy. ► Spontaneous reactions are relatively common in specialized metabolism. ► Enzymes can be engineered for higher rate and substrate specificity. ► Enzymes can be engineered for naturally spontaneous reactions.