Analysis of Biomolecular Condensates in Metabolic Pathways

CD BioSciences is dedicated to the broad functional characterization of biomolecular condensates to develop a range of regulatory targets and approaches to provide new opportunities for drug development and clinical treatment of disease. Here, CD BioSciences offers professional services to analyze the function of biomolecular condensates in metabolic pathways for the development of drug targets.

Introduction

Metabolic reactions are highly organized through spatiotemporal aggregation and compartmentalization of enzymes and substrates/intermediates at subcellular sites, thereby maximizing reaction efficiency. Specifically, transient assembly or segregation of enzymes into clusters allows passage of metabolites, but requires spatiotemporal control. Liquid-liquid phase separation (LLPS) enables the formation of such assemblies into membrane-free organelles (MLOs) that compartmentalize and facilitate cellular biological reactions. MLOs lack lipid bilayers, thus allowing dynamic exchange of reactants and products with the surrounding environment and accelerating intracellular biological reactions. The role of LLPS in the formation of condensates containing the CO₂-fixing enzyme Rubisco has recently become appreciated. It was found that CO₂-fixing regions in cyanobacteria and green algae are metabolic biomolecules condensates.

Fig. 1. The proteins and interactions that underlie Rubisco condensates. (Wunder T, et al., 2020)

Customized Services

The biomolecular condensates themselves attract specific clusters of molecules required for specific metabolic pathways. Examples of metabolic MLOs in mammalian cells remain scarce, thus we focus on metabolic MLOs in eukaryotic algal chloroplasts and yeast cells, attempting to develop their role and potential to influence metabolism through the inclusion and exclusion of specific enzymes.

CD BioSciences is committed to analyzing the metabolic function of biomolecular condensates to enable continuous biochemical reactions mediated by multiple enzymes. We provide potential MLOs associated with metabolism and strategies to discover and characterize them.

• Rubiscosomal Compensation Strategies
  We offer Rubiscosomal compensation strategies to polymerize Rubiscos in biomolecular condensates so that the CO₂ gas at the Rubisco active site is elevated, the enzyme works close to its V_max, and the effects of competing inhibitors and alternative substrates on O₂ are reduced.
• Rubisco Condensation Strategy
  The nature of biomolecular condensates is determined by the structure of their components. We use pure components combined with structural biology approaches to achieve in vitro reconstruction of Rubisco condensates, and to examine the effect of droplets on enzyme concentration and enzymatic reaction rates in vitro.
• Photoinduced Condensation Systems
  We can use light induction in yeast to induce clustering of multiple enzymes, and this clustering can be used to control metabolic fluxes by synthesizing droplets as an assembly of MLOs.

We provide reasonable strategies to try to link LLPS to metabolites experimentally. Based on the metabolic pathways of MLOs, we aim to identify scaffolding proteins that drive the formation of biomolecular condensates in metabolic reactions. Development of scaffolding protein chemistry in these different types of droplets helps clients understand the precise mechanisms of metabolizing MLOs. If you have any special requirements for our services, please feel free to contact us. We are looking forward to working together with your attractive projects.