Self-Assembled Protein-Coated Polyhydroxyalkanoate Beads: Properties and Biomedical Applications

Abstract

Polyhydroxyalkanoates (PHAs) are biological polyesters that can be naturally produced by a range of bacteria as water-insoluble inclusions composed of a PHA core coated with PHA synthesis, structural, and regulatory proteins. These naturally self-assembling shell–core particles have been recently conceived as biomaterials that can be bioengineered as biologically active beads for medical applications. Protein engineering of PHA-associated proteins enabled the production of PHA–protein assemblies exhibiting biologically active protein-based functions relevant for applications as vaccines or diagnostics. Here we provide an overview of the recent advances in bioengineering of PHA particles toward the display of biomedically relevant protein functions such as selected disease-specific antigens as diagnostic tools or for the design of particulate subunit vaccines against infectious diseases such as tuberculosis, meningitis, pneumonia, and hepatitis C.

Polyhydroxyalkanoate‐associated phasins as phylogenetically heterogeneous, multipurpose proteins

“…Early studies carried out by Merrick′s group showed that these inclusions were constituted by approximately 98% (w/w) PHA, 2% granule‐associated proteins (GAPs) and 0.5% phospholipids (Griebel et al ., ). Since then, several studies have confirmed the presence of a phospholipid layer in PHA preparations (Parlane et al ., , and references therein). However, some data have put into question the actual presence of the lipid coat in vivo (Potter and Steinbuchel, ; Beeby et al ., ; Jendrossek and Pfeiffer, ), especially from electron cryotomography (Wahl et al ., ) and fluorescence microscopy (Bresan et al ., ) results, according to which the presence of the lipid layer might arise from an experimental artefact on PHA extraction and preparation.…”

Bioengineered Polyhydroxyalkanoates as Immobilized Enzyme Scaffolds for Industrial Applications

“…PHAs are synthesized by PHA synthases and are deposited as spherical polyester inclusions, which serve as an energy and carbon source (Rehm, 2003(Rehm, , 2010. PHA particles vary in size and range between 100 and 500 nm (Steinmann et al, 2010;Parlane et al, 2016b;Gonzalez-Miro et al, 2019). Poly-(R)-3-hydroxybutyrate (PHB) was the first PHA polymer identified by Lemoigne in 1926 in Bacillus megaterium and is the most common form of PHA FIGURE 1 | Enzyme (shown in green) immobilization via various biological supramolecular assemblies.…”

“…Several promising biological supramolecular assemblies, such as polyhydroxyalkanoate (PHA) particles Parlane et al, 2016b), virus-like particles (VLPs) (Schwarz et al, 2017;Wilkerson et al, 2018), enzyme-derived nanoparticles (EZPs) (Raeeszadeh-Sarmazdeh et al, 2016;Diaz et al, 2018;Schmid-Dannert and López-Gallego, 2019), membrane vesicles Sharma et al, 2018), and magnetosomes (Jacob and Suthindhiran, 2016;Yan et al, 2017) have been studied to immobilize a variety of functional proteins, including industrially relevant enzymes using recombinant fusion technology (Figure 1). Briefly, genetically amenable components of these scaffolds are translationally fused with proteins of interest, such as, e.g., enzymes, and are produced in a range of recombinant expression systems, like various prokaryotic and eukaryotic organisms.…”

Recent Progress in Polyhydroxyalkanoates‐Based Copolymers for Biomedical Applications

“…For example, there are safety concerns associated with live vaccines and viral vectors, as well as the weak immunogenicity and side effects of subunit vaccines. Therefore, an effective antigen carriers to control the location of antigen responses could be important for developing successful and effective vaccines …”

“…Therefore, an effective antigen carriers to control the location of antigen responses could be important for developing successful and effective vaccines. [132][133][134][135] PHA are biopolyester granules produced by the cell endosomes when the carbon source is abundant. During the production of PHA particles, some proteins can be present on the biological beads produced by the bacteria by fusion with the PHA synthase protein.…”