Engineering plant metabolism into microbes: from systems biology to synthetic biology

Xu, Peng; Bhan, Namita; Koffas, Mattheos

doi:10.1016/j.copbio.2012.08.010

Cited by 104 publications

(75 citation statements)

References 70 publications

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“…For example, precursor flux improvement by overexpression of heterologous pathways may not be accommodated by downstream pathways; accumulated or depleted intermediates may compromise cell viability and pathway productivity 13 . As an attempt to address these issues, combinatorial transcriptional engineering coupled with efficient gene assembly tools has offered tremendous opportunities for customized optimization of multi-gene pathways 14 . Excellent examples include creation of yeast xylose pathways by promoter shuffling 15 , heterologous production of anticancer taxol precursors in E. coli 16 and rapid assembly and screening of multi-gene mutant pathway libraries in E. coli and yeast 17,18 .…”

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confidence: 99%

Modular optimization of multi-gene pathways for fatty acids production in E. coli

et al. 2013

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confidence: 99%

Modular optimization of multi-gene pathways for fatty acids production in E. coli

et al. 2013

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“…lant natural products currently have extensive applications in the food and pharmaceutical industries (1,2). Among other things, their unique bioactivities and structures allow them to serve as antimicrobial agents, therapeutic drugs, condiments, and natural dyes (3)(4)(5).…”

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confidence: 99%

Development of a Recombinant Escherichia coli Strain for Overproduction of the Plant Pigment Anthocyanin

Lim

Wong

Bhan

et al. 2015

Appl Environ Microbiol

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bAnthocyanins are water-soluble colored pigments found in terrestrial plants and are responsible for the red, blue, and purple coloration of many flowers and fruits. In addition to the plethora of health benefits associated with anthocyanins (cardioprotective, anti-inflammatory, antioxidant, and antiaging properties), these compounds have attracted widespread attention due to their promising potential as natural food colorants. Previously, we reported the biotransformation of anthocyanin, specifically cyanidin 3-O-glucoside (C3G), from the substrate (؉)-catechin in Escherichia coli. In the present work, we set out to systematically improve C3G titers by enhancing substrate and precursor availability, balancing gene expression level, and optimizing cultivation and induction parameters. We first identified E. coli transporter proteins that are responsible for the uptake of catechin and secretion of C3G. We then improved the expression of the heterologous pathway enzymes anthocyanidin synthase (ANS) and 3-O-glycosyltransferase (3GT) using a bicistronic expression cassette. Next, we augmented the intracellular availability of the critical precursor UDP-glucose, which has been known as the rate-limiting precursor to produce glucoside compounds. Further optimization of culture and induction conditions led to a final titer of 350 mg/liter of C3G. We also developed a convenient colorimetric assay for easy screening of C3G overproducers. The work reported here constitutes a promising foundation to develop a cost-effective process for large-scale production of plant-derived anthocyanin from recombinant microorganisms.

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“…Its overriding focus is to take a holistic view of the structure and dynamics of organisms, rather than to pursue the arguably more conventional reductionist approach. Systems biology has helped in summarizing huge disparate data sets and testing their consistency (Xu et al, 2013b). Efforts to adopt this approach for plant studies have led to the concept of the "in silico plant" (Raikhel and Coruzzi, 2003).…”

Section: Systems Biological Approach Toward Understanding Plant Metabmentioning

confidence: 99%

“…While engineering prokaryotic metabolism is a well-developed technology, its status in plants lags behind (Morgan and Rhodes, 2002;Toya and Shimizu, 2013;Xu et al, 2013b), mainly because of the extremely large diversity of metabolites present within plants compared with other organisms (Fernie et al, 2011). Such diversity implies a highly complex network of metabolic pathways, requiring sophisticated over-arching control by supercoordinated gene-metabolic interaction networks (Aharoni and Galili, 2011).…”

Section: Introductionmentioning

confidence: 99%

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Plant Metabolic Modeling: Achieving New Insight into Metabolism and Metabolic Engineering

2014

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Models are used to represent aspects of the real world for specific purposes, and mathematical models have opened up new approaches in studying the behavior and complexity of biological systems. However, modeling is often time-consuming and requires significant computational resources for data development, data analysis, and simulation. Computational modeling has been successfully applied as an aid for metabolic engineering in microorganisms. But such model-based approaches have only recently been extended to plant metabolic engineering, mainly due to greater pathway complexity in plants and their highly compartmentalized cellular structure. Recent progress in plant systems biology and bioinformatics has begun to disentangle this complexity and facilitate the creation of efficient plant metabolic models. This review highlights several aspects of plant metabolic modeling in the context of understanding, predicting and modifying complex plant metabolism. We discuss opportunities for engineering photosynthetic carbon metabolism, sucrose synthesis, and the tricarboxylic acid cycle in leaves and oil synthesis in seeds and the application of metabolic modeling to the study of plant acclimation to the environment. The aim of the review is to offer a current perspective for plant biologists without requiring specialized knowledge of bioinformatics or systems biology.

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Engineering plant metabolism into microbes: from systems biology to synthetic biology

Cited by 104 publications

References 70 publications

Modular optimization of multi-gene pathways for fatty acids production in E. coli

Modular optimization of multi-gene pathways for fatty acids production in E. coli

Development of a Recombinant Escherichia coli Strain for Overproduction of the Plant Pigment Anthocyanin

Plant Metabolic Modeling: Achieving New Insight into Metabolism and Metabolic Engineering

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