Encapsulation as a Strategy for the Design of Biological Compartmentalization

Abstract

Compartmentalization is one of the defining features of life. Through intracellular spatial control, cells are able to organize and regulate their metabolism. One of the most broadly used organizational principles in nature is encapsulation. Cellular processes can be encapsulated within either membrane-bound organelles or proteinaceous compartments that create distinct microenvironments optimized for a given task. Further challenges addressed through intracellular compartmentalization are toxic or volatile pathway intermediates, slow turnover rates and competing side reactions. This review highlights a selection of naturally occurring membrane- and protein-based encapsulation systems in microbes and their recent applications and emerging opportunities in synthetic biology. We focus on examples that use engineered cellular organization to control metabolic pathway flux for the production of useful compounds and materials.

A Catalytic Nanoreactor Based on in Vivo Encapsulation of Multiple Enzymes in an Engineered Protein Nanocompartment

“…Compartmentalization of biochemical pathways and other biological processes is a key feature of all cells . Complex metabolism relies on the spatial control of often concurrent incompatible reactions at any given time.…”

Engineering the Bacterial Microcompartment Domain for Molecular Scaffolding Applications

“…Biological engineers have increasingly explored a variety of rational colocalization strategies to capitalize on such benefits. These engineered systems range in complexity from simple fusion proteins to dynamic artificial scaffolds (Conrado et al, 2008; Horn and Sticht, 2015; Myhrvold and Silver, 2015) or compartments (Giessen and Silver, 2016). As biologists move toward increasingly complex cellular engineering goals (Bashor et al, 2010), one challenge is designing sophisticated subcellular colocalization approaches that recapitulate the elegance of natural systems (Good et al, 2011).…”

Self‐Assembly and Stabilization of Hybrid Cowpea Chlorotic Mottle Virus Particles under Nearly Physiological Conditions

“…So far, we have not succeeded at fully disassembling capsids formed by this more hydrophobic variant. This may be problematic for cargo loading, although a solution could be to employ in vivo cargo loading during capsid protein expression, which is common practice for several other VLPs . Remaining challenges for future research are the further improvement of the stability of the ELP[Y 2 V 2 L 4 G 1 ‐9] variant and to find other ways for encapsulating cargo inside capsids formed by the ELP[W 2 V 2 L 4 G 1 ‐9] variant.…”