Synthetic Biology Parts, Devices and Applications

14.2 On Organelles 281

14.2 On Organelles

Advances in imaging and comparative genomics have muddled the latter twenti­
eth‐century definition of an organelle as a specialized lipid‐enclosed compart­
ment found only in eukaryotes [20, 21]. It is now clear that many prokaryotes
contain topologically distinct membrane compartments and that proteinaceous
BMCs also found in prokaryotes possess metabolic features similar to complex
structures such as mitochondria [9, 22]. In the early years of light microscopy,
beginning with Möbius in the late 1800s, many cytoplasmic features including
ribosomes, flagella, and the centriole were labeled with the diminutive organelle.
Given recent results and historically ambiguity, we therefore propose to adapt a
more relaxed definition in the context of this review: an organelle is simply a
physically delimited compartment within the cell.
An alternative viewpoint, particularly for the synthetic biologist, is to ask what
is required to repurpose an existing organelle or construct one de novo. In this
light, four important intertwined, but distinct, themes emerge (Figure 14.2). The
first is targeting. To accomplish orthogonal function in a specific compartment,
it is essential to have selective targeting of biochemical activities (i.e., typically
enzymes). Nature widely leverages the specificity inherent to protein–protein
interactions through the use of signal sequences. Engineering an organelle
requires extensive knowledge of targeting, specificity of this process, and ideally,
how the stoichiometry of targeted components can be adjusted to control
activity of individual proteins.

100 100 101

100 nm

Carboxysome

Encapsulin

10 nm 20 nm

Complexity

# of genes

Physical size

Tryptophan

synthase

Enzymes

Microcompartments

Nano

compartments Repurposedorganelles/kleptoplasty

Hijacked

mitochondria

Synthetic consortia

Celluose-degrading culture

0.1–10 μm 1–10 μm

102 –10^3103 –10^4

Figure 14.1 Possible strategies for engineering a synthetic organelle. Complexity of intra‐ and
intercellular spatial organization spans from enzymes with inherent substrate channeling to
symbiotic cocultures. This review highlights work in the middle ground, from
nanocompartments to repurposed organelles.