Substrate Partitioning into Protein Macromolecular Frameworks for Enhanced Catalytic Turnover

• Published in: ACS nano Vol. 15; no. 10; pp. 15687 - 15699
• Main Authors: Selivanovitch, Ekaterina, Uchida, Masaki, Lee, Byeongdu, Douglas, Trevor
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 26-10-2021; American Chemical Society (ACS)
• Subjects: Catalysis; catalytic material; dendrons; emergent property; heterogeneous catalyst; imaging probes; INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; ionic strength; lattices; Macromolecular Substances; Osmolar Concentration; partition coefficient; peptides and proteins; protein macromolecular framework (PMF); Scattering, Small Angle; virus-like particle (VLP); X-Ray Diffraction; heterogeneous catalyst; partition coefficient; protein macromolecular framework (PMF); emergent property; virus-like particle (VLP); catalytic material
• ISSN: 1936-0851; 1936-086X
• DOI: 10.1021/acsnano.1c05004

Spatial partitioning of chemical processes is an important attribute of many biological systems, the effect of which is reflected in the high efficiency of enzymes found within otherwise chaotic cellular environments. Barriers, often provided through the formation of compartments or phase segregation, gate the access of macromolecules and small molecules within the cell and provide an added level of metabolic control. Taking inspiration from nature, we have designed virus-like particles (VLPs) as nanoreactor compartments that sequester enzyme catalysts and have used these as building blocks to construct 3D protein macromolecular framework (PMF) materials, which are structurally characterized using small-angle X-ray scattering (SAXS). The highly charged PMFs form a separate phase in suspension, and by tuning the ionic strength, we show positively charged molecules preferentially partition into the PMF, while negatively charged molecules are excluded. This molecular partitioning was exploited to tune the catalytic activity of enzymes enclosed within the individual particles in the PMF, the results of which showed that positively charged substrates had turnover rates that were 8500× faster than their negatively charged counterparts. Moreover, the catalytic PMF led to cooperative behavior resulting in charge dependent trends opposite to those observed with individual P22 nanoreactor particles.