With the impending fossil fuel crisis, the search for and development of alternative chemical/material substitutes is pivotal in reducing mankind's dependency on fossil resources. One of the ...potential substitute candidates is polyhydroxyalkanoate (PHA). PHA is a carbon-neutral and valuable polymer that could be produced from many renewable carbon sources by microorganisms, making it a sustainable and environmental-friendly material. At present, PHA is not cost competitive compared to fossil-derived products. Encouraging and intensifying research work on PHA is anticipated to enhance its economic viability in the future. The development of various biomolecular and chemical techniques for PHA analysis has led to the identification of many PHA-producing microbial strains, some of which are deposited in culture collections. Research work on PHA could be rapidly initiated with these ready-to-use techniques and microbial strains. This review aims to facilitate the start-up of PHA research by providing a summary of commercially available PHA-accumulating microbial cultures, PHA biosynthetic pathways, and methods for PHA detection, extraction and analysis.
Nowadays, we are witnessing highly dynamic research activities related to the intriguing field of biodegradable materials with plastic-like properties. These activities are currently intensified by a ...strengthened public awareness of prevailing ecological issues connected to growing piles of plastic waste, microplastic formation, and increasing greenhouse gas emissions; this goes hand-in-hand with the ongoing depletion of fossil feedstocks, which are traditionally used to produce full carbon backbone polymers. To a steadily increasing extend, polyhydroxyalkanoate (PHA) biopolyesters, a family of plastic-like materials with versatile material properties, are considered a future-oriented solution for diminishing these concerns. PHA production is based on renewable resources, and occurs in a bio-mediated fashion by the action of living organisms. If accomplished in an optimized way, PHA production and the entire PHA lifecycle are embedded into nature´s closed cycles of carbon. Holistic improvement of PHA production, applicable on an industrially relevant scale, calls for inter alia: consolidated knowledge about the enzymatic and genetic particularities of PHA accumulating organisms, in-depth understanding of the kinetics of the bioprocess, the selection of appropriate inexpensive fermentation feedstocks, tailoring the composition of PHA on the level of the monomeric constituents, optimized biotechnological engineering, and novel strategies for PHA recovery from biomass characterized by minor energy and chemical requirement.
In the modern era, nanomedicine has developed novel drug-delivery strategies to improve chemotherapy. Nanotechnological-based treatment approaches for cancer through targeted tumour drug delivery and ...stimulus-responsive tumour microenvironment have gained tremendous success in oncology. The application of building block materials of these nanomedicines plays a vital role in cancer remediation. Despite successful application in various medical treatments, nanocarriers' lack of biodegradability and biocompatibility makes their use in a clinical context difficult. In addition, the preparation of current drug delivery systems is a major constraint. The current cancer treatment methods aim to destroy diseased tissue, frequently with the use of radiation and chemotherapy. These treatment options are accompanied by a significant level of toxicity, which has excellent potential to further medical issues in the afflicted patient. Polyhydroxyalkanoate (PHA) polymers are biodegradable and biocompatible polyesters that can potentially be used as nanoparticular delivery systems for cancer treatment. Previously, PHA has shown tremendous application as a packaging material in the food and pharma industry. PHA-based nanocarriers are an effective drug delivery system because of their non-immunogenicity, regulated drug release, high drug loading capacity, and targeted drug delivery. This review focuses on creating and using PHA-based nanocarriers in cancer treatment. Despite its many benefits, PHA-based nanocarriers have yet to progress to clinical trials for drug delivery applications due to several issues, including the polymers' hydrophobic nature and high production costs. This review examines these challenges along with existing alternatives.
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•A significant level of toxicity accompanies the conventional oncological treatment options.•Polyhydroxyalkanoate (PHA) polymers may serve as potential nanoparticular delivery systems for cancer chemotherapy.•The physicochemical properties of PHAs promote various vital cellular processes and activity in tissues.•PHA copolymer-based nanocarriers play significant roles in drug delivery for cancer treatment.•This review focuses on various challenges associated with PHA nanocarrier synthesis and its drug delivery efficacy.
Biodegradation of short-chain-length polyhydroxyalkanoates (scl-PHAs) and medium-chain-length polyhydroxyalkanoates (mcl-PHAs) was studied using 2 bacteria, Pseudomonas chlororaphis and Acinetobacter ...lwoffii, which secrete an enzyme, or enzymes, with lipase activity. These bacteria produced clear zones of depolymerization on Petri plates containing colloidal solutions of PHA polymers with different monomer compositions. Lipase activity in these bacteria was measured using p-nitrophenyl octanoate as a substrate. In liquid medium, scl-PHA (e.g., PHBV) and mcl-PHA (e.g., PHO) films were used as the sole carbon source for growth, and after 7 days, 5%–18% loss in mass of PHA films was observed. Scanning electron microscopy of these films revealed bacterial colonization of the polymers, with cracks and pitting in the film surfaces. Degradation of polymers released 3-hydroxyhexanoate, 3-hydroxyoctanoate, and 3-hydroxydecanoate monomers into the liquid medium, depending on the starting polymer. Genes encoding secretory lipases, with amino acid consensus sequences for lipase boxes and oxyanion holes, were identified in the genomes of P. chlororaphis and A. lwoffii. Although amino acid consensus sequences for lipase boxes and oxyanion holes are also present in PHA depolymerases identified in the genomes of other PHA-degrading bacteria, the P. chlororaphis and A. lwoffii lipases had low homology with these depolymerases.
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•Pseudomonas umsongensis GO16 is a metabolically versatile bacterium.•GO16 grows with waste-derived substrates (hydrolysed PET, glycerol, butyrate etc.)•GO16 produces a blend of short ...and medium chain length polyhydroxyalkanoates PHA.•PHAs are blended on the level of PHA granule in GO16.•PHA blends offer better mechanical and physical properties.
Polyhydroxyalkanoates (PHAs) are biological polyesters, viewed as a replacement for petrochemical plastic. However, they suffer from suboptimal physical and mechanical properties. Here, it was shown that a metabolically versatile Pseudomonas umsongensis GO16 can synthesise a blend of short chain length (scl) and medium chain length (mcl)-PHA. A defined mix of butyric (BA) and octanoic acid (OA) in different ratios was used. The PHA monomer composition varied depending on the feeding strategy. When OA and BA were fed at 80:20 ratio it showed 14, 8, 77 and 1 mol% of (R)-3-hydroxybutyrate, (R)-3-hydroxyhexanoate, (R)-3-hydroxyoctanoate and (R)-3-hydroxydecanoate respectively. The polymer characterisation clearly shows that polyhydroxybutyrate (PHB) and mcl-PHA are produced individually. The two polymers are blended on the PHA granule level, as demonstrated by fluorescence microscopy and yeast two-hybrid assay. The resulting blend has a specific viscoelasticity compared to PHB and PHO. Mcl-PHA acts as a plasticiser and reduces PHB brittleness.
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•Four PHA producing Antarctic bacterial isolates were studied through whole-genome sequence analysis.•A potentially new class of PHA synthase (PhaC) was identified from Antarctic ...bacterial isolates through the analysis.•The new class of PhaC was proven to be functional through in vivo and in vitro assays.•There may be more types of PhaCs than the four classes that are currently known.
The polyhydroxyalkanoate (PHA) producing capability of four bacterial strains isolated from Antarctica was reported in a previous study. This study analyzed the PHA synthase genes and the PHA-associated gene clusters from the two antarctic Pseudomonas isolates (UMAB-08 and UMAB-40) and the two antarctic Janthinobacterium isolates (UMAB-56 and UMAB-60) through whole-genome sequence analysis. The Pseudomonas isolates were found to carry PHA synthase genes which fall into two different PHA gene clusters, namely Class I and Class II, which are involved in the biosynthesis of short-chain-length-PHA (SCL-PHA) and medium-chain-length-PHA (MCL-PHA), respectively. On the other hand, the Janthinobacterium isolates carry a Class I and an uncharacterized putative PHA synthase genes. No other gene involved in PHA synthesis was detected in close proximity to the uncharacterized putative PHA synthase gene in the Janthinobacterium isolates, therefore it falls into a separate clade from the ordinary Class I, II, III and IV clades of PHA synthase (PhaC) phylogenetic tree. Multiple sequence alignment showed that the uncharacterized putative PHA synthase gene contains all the highly conserved amino acid residues and the proposed catalytic triad of PHA synthase. PHA biosynthesis and in vitro PhaC enzymatic assay results showed that this uncharacterized putative PHA synthase from Janthinobacterium sp. UMAB-60 is funtional. This report adds new knowledge to the PHA synthase database as we describe scarce information of PHA synthase genes and PHA-associated gene clusters from the antarctic bacterial isolates (extreme and geographically isolated environment) and comparing with those from non-antarctic PHA-producing bacteria.
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•Polyhydroxyalkanoates a potential biopolymer substitute for conventional plastics.•Critically reviewed various waste streams for sustainable and inexpensive PHA production.•Recent ...advances on fermentation strategies & synthetic biology for higher PHA production.•Discussed PHA- nanocomposites and their application in various sectors.•Future perspectives & technical challenges for efficient waste-bioplastic production addressed.
Polyhydroxyalkanoates (PHA) are appealing as an important alternative to replace synthetic plastics owing to its comparable physicochemical properties to that of synthetic plastics, and biodegradable and biocompatible nature. This review gives an inclusive overview of the current research activities dealing with PHA production by utilizing different waste fluxes generated from food, milk and sugar processing industries. Valorization of these waste fluxes makes the process cost effective and practically applicable. Recent advances in the approaches adopted for waste treatment, fermentation strategies, and genetic engineering can give insights to the researchers for future direction of waste to bioplastics production. Lastly, synthesis and application of PHA-nanocomposites, research and development challenges, future perspectives for sustainable and cost-effective PHB production are also discussed. In addition, the review addresses the useful information about the opportunities and confines associated with the sustainable PHA production using different waste streams and their evaluation for commercial implementation within a biorefinery.
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•Halomonas isolates ASL10 and ASL10 can produce PHA by using cost effective algal hydrolysates media.•The utilization of C. mediterranea hydrolysates as C and N sources yielded the ...maximum PHA concentrations.•PHA-NPs showed a new antibacterial attribute against several reference strains.•PHA-NPs revealed relatively low hemolysis which affirms the safety of the proposed NPs for different applications.
Algae are omnipresent in all seas and oceans, which make thema target for many applications such as bio-fertilizers, fish feeding and removal of heavy metals. In the present study, different algal species were examined as sustainable alternatives substrates for PHA production by Halomonas sp. Several media simulations were utilized to achieve high polymer productivity. The maximum poly(3-hydroxybutyrate) (PHB) concentrations were determined by using Corallina mediterranea hydrolysates as a carbon and nitrogen source. The isolates Halomonas pacifica ASL10 and Halomonas salifodiane ASL11 were found to be able to produce PHA by 67 % wt and 63 % wt CDW, respectively. PHB nanoparticles (NPs) had high zeta potential values and small particle sizes. These properties make it suitable for several drug delivery and pharmaceutical applications. Interestingly, NPs showed a potent antibacterial activity against several reference strains. The antibacterial efficacy of PHA-NPs has not been previously studied, thus this study opens a promising use of PHA-NPs.
Microbial polyhydroxyalkanoates (PHA) containing short‐ and medium/long‐chain‐length monomers, abbreviated as SCL‐co‐MCL/LCL PHAs, generate suitable thermal and mechanical properties. However, ...SCL‐co‐MCL/LCL PHAs with carbon chain longer than nine are difficult to synthesize due to the low specificity of PHA synthase PhaC and the lack of either SCL‐ or MCL/LCL monomer precursor fluxes. This study succeeds in reprogramming a β‐oxidation weakened Pseudomonas entomophila containing synthesis pathways of SCL 3‐hydroxybutyryl‐CoA (3HB) from glucose and MCL/LCL 3‐hydroxyalkanoyl‐CoA from fatty acids with carbon chain lengths from 9 to 18, respectively, that are polymerized under a low specificity PhaC61‐3 to form P(3HB‐co‐MCL/LCL 3HA) copolymers. Through rational flux‐tuning approaches, the optimized recombinant P. entomophila accumulates 55 wt% poly‐3‐hydroxybutyrate in 8.4 g L−1 cell dry weight. Combined with weakened β‐oxidation, a series of novel P(3HB‐co‐MCL/LCL 3HA) copolymers with over 60 wt% PHA in 9 g L−1 cell dry weight have been synthesized for the first time. P. entomophila has become a high‐performing platform to generate tailor‐made new SCL‐co‐MCL/LCL PHAs.
A high‐performing bacterial platform for customized SCL‐co‐MCL/LCL PHA synthesis is developed via rational fine‐tuning approaches, based on which, a series of P(3HB‐co‐MCL/LCL 3HA) copolymers are generated with 3HA ranging from 9 to 18 carbon atoms. The PHA copolymer family is thus further expanded, generating various novel material properties and broader prospects for value‐added applications.
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