With the rapid development of synthetic biology, various kinds of microbial cell factories (MCFs) have been successfully constructed to produce high-value-added compounds. However, the complexity of metabolic regulation and pathway crosstalk always cause issues such as intermediate metabolite accumulation, byproduct generation, and metabolic burden in MCFs, resulting in low efficiencies and low yields of industrial biomanufacturing. Such issues could be solved by spatially rearranging the pathways using intracellular compartments. In this review, design strategies are summarized and discussed based on the types and characteristics of natural and artificial subcellular compartments. This review systematically presents information for the construction of efficient MCFs with intracellular compartments in terms of four aspects of design strategy goals: (1) improving local reactant concentration; (2) intercepting and isolating competing pathways; (3) providing specific reaction substances and environments; and (4) storing and accumulating products.
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http://dx.doi.org/10.1021/acssynbio.2c00671 | DOI Listing |
JIMD Rep
January 2025
The Morris Kahn Laboratory of Human Genetics, Faculty of Health Sciences Ben Gurion University Beer-Sheva Israel.
The tightly-regulated spatial and temporal distribution of zinc ion concentrations within cellular compartments is controlled by two groups of Zn transporters: the 14-member ZIP/SLC39 family, facilitating Zn influx into the cytoplasm from the extracellular space or intracellular organelles; and the 10-member ZnT/SLC30 family, mobilizing Zn in the opposite direction. Genetic aberrations in most zinc transporters cause human syndromes. Notably, previous studies demonstrated osteopenia and male-specific cardiac death in mice lacking the ZnT5/ zinc transporter, and suggested association of two homozygous frameshift variants with perinatal mortality in humans, due to hydrops fetalis and hypertrophic cardiomyopathy.
View Article and Find Full Text PDFPLoS One
January 2025
ESQlabs Gmbh, Saterland, Germany.
Digital twins, driven by data and mathematical modelling, have emerged as powerful tools for simulating complex biological systems. In this work, we focus on modelling the clearance on a liver-on-chip as a digital twin that closely mimics the clearance functionality of the human liver. Our approach involves the creation of a compartmental physiological model of the liver using ordinary differential equations (ODEs) to estimate pharmacokinetic (PK) parameters related to on-chip liver clearance.
View Article and Find Full Text PDFBackground: This study investigates the impact of IGC-AD1, a combination comprising of low concentration of delta-9 tetrahydrocannabinol ("THC") and melatonin on blood serum potassium levels in patients with Alzheimer's disease ("AD"). Loss of intracellular compartmentalization of potassium is a characteristic of AD pathology, with supporting studies indicating significantly lower potassium levels in intracellular compartments of AD brains and an associated increase in serum potassium levels in AD subjects. Here, we present preliminary safety lab data from a Phase I trial of AD patients administered with IGC-AD1.
View Article and Find Full Text PDFBackground: Aβ accumulation is a key event driving neurotoxicity in Alzheimer's disease. Previously, we demonstrated that oligomers of amyloid beta (oAβ) induce an increase in the levels of APP and BACE1 in Rab11-positive endosomes, leading to the intracellular accumulation of Aβ1-42 in human neurons derived from iPSCs (HN-iPSCs). This vicious cycle of Aβ generation induced by Aβ itself, is pivotal for the propagation of pathology.
View Article and Find Full Text PDFJ Am Chem Soc
January 2025
The State Key Laboratory of Molecular Engineering of Polymers and Department of Macromolecular Science, Fudan University, Shanghai 200438, P. R China.
Designing artificial enzymes for in vivo catalysis presents a great challenge due to biomacromolecule contamination, poor biodistribution, and insufficient substrate interaction. Herein, we developed single-chain polymeric nanoparticles with Cu/N-heterocyclic carbene active sites (SCNP-Cu) to function as peroxidase mimics for in vivo catalysis and chemo-dynamic therapy (CDT). Compared with the enzyme mimics based on unfolded linear polymer scaffold and multichain cross-linked scaffold, SCNP-Cu exhibits improved tumor accumulation and CDT efficiency both in vitro and in vivo.
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