Abstract
Malonyl-CoA is the basic building block for synthesizing a range of important compounds including fatty acids, phenylpropanoids, flavonoids and non-ribosomal polyketides. Centering around malonyl-CoA, we summarized here the various metabolic engineering strategies employed recently to regulate and control malonyl-CoA metabolism and improve cellular productivity. Effective metabolic engineering of microorganisms requires the introduction of heterologous pathways and dynamically rerouting metabolic flux towards products of interest. Transcriptional factor-based biosensors translate an internal cellular signal to a transcriptional output and drive the expression of the designed genetic/biomolecular circuits to compensate the activity loss of the engineered biosystem. Recent development of genetically-encoded malonyl-CoA sensor has stood out as a classical example to dynamically reprogram cell metabolism for various biotechnological applications. Here, we reviewed the design principles of constructing a transcriptional factor-based malonyl-CoA sensor with superior detection limit, high sensitivity and broad dynamic range. We discussed various synthetic biology strategies to remove pathway bottleneck and how genetically-encoded metabolite sensor could be deployed to improve pathway efficiency. Particularly, we emphasized that integration of malonyl-CoA sensing capability with biocatalytic function would be critical to engineer efficient microbial cell factory. Biosensors have also advanced beyond its classical function of a sensor actuator for in situ monitoring of intracellular metabolite concentration. Applications of malonyl-CoA biosensors as a sensor-invertor for negative feedback regulation of metabolic flux, a metabolic switch for oscillatory balancing of malonyl-CoA sink pathway and source pathway and a screening tool for engineering more efficient biocatalyst are also presented in this review. We envision the genetically-encoded malonyl-CoA sensor will be an indispensable tool to optimize cell metabolism and cost-competitively manufacture malonyl-CoA-derived compounds.
Highlights
Photon counting X-ray spectrometers that can operate in harsh environments are increasingly important for extreme terrestrial and space exploration applications
Al0.52In0.48P has an indirect bandgap of 2.31 eV [7]; AlxIn1−xP with different Al fractions correspond to different bandgaps: in principle, the Al fraction can vary from 0, corresponding to a bandgap of 2.5 eV, to 1, corresponding to a bandgap of 1.34 eV
The average energy consumed in the generation of an electron–hole pair in Al0.52In0.48P was measured at room temperature (20 ◦C), using a custom Al0.52In0.48P X-ray photodiode, an 55Fe radioisotope X-ray source, custom low-noise charge-sensitive preamplifier electronics, and a high-purity reference GaAs X-ray photodiode
Summary
Photon counting X-ray spectrometers that can operate in harsh environments (high temperature, intense radiation) are increasingly important for extreme terrestrial and space exploration applications. Wide bandgap semiconductors, such as GaAs [1,2], AlGaAs [3], and SiC [4], have been investigated as detector materials for such X-ray spectrometers. Al0.52In0.48P has a high effective atomic number, and relatively high linear X-ray attenuation coefficient, as a consequence of the presence of Indium (atomic number 49) [9] This results in higher X-ray quantum efficiency per unit thickness [5] compared to some other wide bandgap X-ray photodetectors, e.g. SiC, AlGaAs, and GaAs [10,11]. It must be underlined that the energy consumed in the generation of an electron–hole pair at X-ray energies in a semiconductor differs from its bandgap; whilst the Al0.52In0.48P bandgap is well known [7], until now there have been no experimental measurements of εAlInP
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