* Negative feedback regulation of fatty acid production based on a malonyl-CoA sensor-actuator.
- Engineering metabolic biosynthetic pathways has enabled the microbial production of many useful chemicals. However, pathway productivities and yields are often limited by metabolic imbalances. Synthetic regulatory circuits have been shown to be able to balance engineered pathways, improving titers and productivities. Here we developed a negative feedback regulatory circuit based on a malonyl-CoA-based sensor-actuator. Malonyl-CoA is biosynthesized from acetyl-CoA by the acetyl-CoA carboxylase, which is the rate-limiting step for fatty acid biosynthesis. Overexpression of acetyl-CoA carboxylase improves fatty acid production, but slows down cell growth. We have devised a malonyl-CoA sensor-actuator that controls gene expression levels based on intracellular malonyl-CoA concentrations. This sensor-actuator is used to construct a negative feedback circuit to regulate the expression of acetyl-CoA carboxylase. The negative feedback circuit is able to up-regulate acetyl-CoA carboxylase expression when the malonyl-CoA concentration is low and down-regulate acetyl-CoA carboxylase expression when excess amounts of malonyl-CoA have accumulated. We show that the regulatory circuit effectively alleviates the toxicity associated with acetyl-CoA carboxylase overexpression. When used to regulate the fatty acid pathway, the feedback circuit increases fatty acid titer and productivity by 34% and 33%, respectively.
=>茂み, 成長, 増加, 発展, 栽培, 腫よう, 成長物
Overview of noun growth
The noun growth has 7 senses (first 5 from tagged texts)
1. (37) growth, growing, maturation, development, ontogeny, ontogenesis -- ((biology) the process of
an individual organism growing organically; a purely biological unfolding of events involved in an
organism changing gradually from a simple to a more complex level; "he proposed an indicator of
osseous development in children")
2. (20) growth -- (a progression from simpler to more complex forms; "the growth of culture")
3. (3) increase, increment, growth -- (a process of becoming larger or longer or more numerous or
more important; "the increase in unemployment"; "the growth of population")
4. (3) growth -- (vegetation that has grown; "a growth of trees"; "the only growth was some salt
grass")
5. (1) emergence, outgrowth, growth -- (the gradual beginning or coming forth; "figurines presage
the emergence of sculpture in Greece")
6. growth -- ((pathology) an abnormal proliferation of tissue (as in a tumor))
7. growth -- (something grown or growing; "a growth of hair")
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