A strategy for the regulation of enzyme cascade reaction efficiency by a DNA machine in vitro is presented. Two cascade enzymes (GOx and HRP) are attached to the DNA machine, and the enzyme cascade reaction shows much higher efficiency when the two enzymes are brought closer by the DNA machine than when they are distant.

No abstract

The Warburg effect, characterized by increased glucose uptake and lactate production, is a well-known universal across cancer cells and other proliferating cells. PKM2, a splice isoform of the pyruvate kinase (PK) specifically expressed in these cells, serves as a major regulator of this metabolic reprogramming with an adjustable activity subjected to numerous allosteric effectors and posttranslational modifications. Here, we have identified a posttranslational modification on PKM2, GlcNAcylation, which specifically targets Thr and Ser, residues of the region encoded by the alternatively spliced exon 10 in cancer cells. We show that PKM2 GlcNAcylation is up-regulated in various types of human tumor cells and patient tumor tissues. The modification destabilized the active tetrameric PKM2, reduced PK activity, and led to nuclear translocation of PKM2. We also observed that the modification was associated with an increased glucose consumption and lactate production and enhanced level of lipid and DNA synthesis, indicating that GlcNAcylation promotes the Warburg effect. In vivo experiments showed that blocking PKM2GlcNAcylation attenuated tumor growth. Thus, we demonstrate that GlcNAcylation is a regulatory mechanism for PKM2 in cancer cells and serves as a bridge between PKM2 and metabolic reprogramming typical of the Warburg effect.

The DNA origami technique has empowered a new paradigm in plasmonics for manipulating light and matter at the nanoscale. This interdisciplinary field has witnessed vigorous growth, outlining a viable route to construct advanced plasmonic architectures with tailored optical properties. However, so far plasmonic systems templated by DNA origami have been restricted to respond to only single stimuli. Despite broad interest and scientific importance, thermal and aptamer-target regulations have not yet been widely utilized to reconfigure three-dimensional plasmonic architectures. In this Letter, we demonstrate a chiral plasmonic nanosystem integrated with split aptamers, which can respond to both thermal and aptamer-target regulations. We show that our dualresponsive system can be noninvasively tuned in a wide range of temperatures, readily correlating thermal control with optical signal changes. Meanwhile, our system can detect specific targets including adenosine triphosphate and cocaine molecules, which further enhance the optical response modulations and in turn influence the thermal tunability.

One of the fundamental challenges in nanophotonics is to gain full control over nanoscale optical elements. The precise spatiotemporal arrangement determines their interactions and collective behavior. To this end, DNA nanotechnology is employed as an unprecedented tool to create nanophotonic devices with excellent spatial addressability and temporal programmability. However, most of the current DNA-assembled nanophotonic devices can only reconfigure among random or very few defined states. Here, we demonstrate a DNA-assembled rotary plasmonic nanoclock. In this system, a rotor gold nanorod can carry out directional and reversible 360° rotation with respect to a stator gold nanorod, transitioning among 16 well-defined configurations powered by DNA fuels. The full-turn rotation process is monitored by optical spectroscopy in real time. We further demonstrate autonomous rotation of the plasmonic nanoclock powered by DNAzyme-RNA interactions. Such assembly approaches pave a viable route towards advanced nanophotonic systems entirely from the bottom-up.