2016
DOI: 10.1016/j.tibtech.2016.02.010
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Metabolic Burden: Cornerstones in Synthetic Biology and Metabolic Engineering Applications

Abstract: Engineering cell metabolism for bioproduction not only consumes building blocks and energy molecules (e.g., ATP) but also triggers energetic inefficiency inside the cell. The metabolic burdens on microbial workhorses lead to undesirable physiological changes, placing hidden constraints on host productivity. We discuss cell physiological responses to metabolic burdens, as well as strategies to identify and resolve the carbon and energy burden problems, including metabolic balancing, enhancing respiration, dynam… Show more

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Cited by 528 publications
(398 citation statements)
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“…Since this engineered strain is plasmid free, and the heterologous pathway is controlled by a constitutive promoter, the production of mevalonate is genetically stable and inducer free, which has potential for scale-up fermentation (15,36). We enhanced the glycolytic flux by deleting the atpFH genes to improve productivity.…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…Since this engineered strain is plasmid free, and the heterologous pathway is controlled by a constitutive promoter, the production of mevalonate is genetically stable and inducer free, which has potential for scale-up fermentation (15,36). We enhanced the glycolytic flux by deleting the atpFH genes to improve productivity.…”
Section: Discussionmentioning
confidence: 99%
“…Although plasmid-based production of mevalonate achieved high yields, the disadvantages of plasmid-based fermentation pose significant challenges for large-scale fermentation (11)(12)(13)(14)(15). First, the replication of plasmid and expression of the genes residing on the plasmid result in extra metabolic burden, which reduces the allocation of nutrient and energy resources for the desired product (12).…”
mentioning
confidence: 99%
“…In engineered microbes harboring heterologous pathways, increased metabolic burden (Wu et al, 2016) and unexpected impacts on endogenous metabolism make the isolated study of metabolite toxicity difficult. To avoid this complexity, most studies have relied on well-controlled systems where the toxic product is exogenously added to the wild-type host and systems analyses are employed to study the stress response (Brynildsen and Liao, 2009).…”
Section: Introductionmentioning
confidence: 99%
“…Even if the compound is transported, it is unclear if the stress response associated with exogenous addition reflects the response associated with in vivo production. This is particularly true for a wild type host, which likely has different metabolism and overall fitness compared to an extensively engineered production strain (Wu et al, 2016). Finally, exogenous addition can introduce unintended artifacts or impurities to the experimental system.…”
Section: Introductionmentioning
confidence: 99%
“…However, the majority of bioproduction processes are still struggling with low yield and productivity, and high production cost which limit their industrial application. Redox imbalance (Chen et al, 2014;van Hoek and Merks, 2012), by-production formation (Arshad et al, 2008;Lee et al, 2001) and metabolic burden (Wu et al, 2016) are often seen thorny problems during bioproduction processes. Solving these issues and increasing its competitiveness against chemical production processes, has attracted plenty of research interests.…”
Section: Introductionmentioning
confidence: 99%