Grand Challenges for Industrializing Polyhydroxyalkanoates (PHAs)

Tan, Dan; Wang, Ying; Tong, Yi; Chen, Guo‐Qiang

doi:10.1016/j.tibtech.2020.11.010

Cited by 191 publications

(127 citation statements)

References 82 publications

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“…However, the PHA synthase with different specificity of substrates is the key enzyme to determine the diversity of monomer structure of PHA chains ( Jung et al, 2010 ; Chen et al, 2016 ; Zhang et al, 2020 ). The molar ratio of each polymerization units can be easily moderated by controlling either the addition dosage of structure-related carbon sources or expression level of targeted synthesis pathways ( Aldor and Keasling, 2003 ; Wang et al, 2019 ; Tan et al, 2020 ). A list of various PHA production by commonly used recombinant engineered chassis from different carbon sources was briefly summarized in Table 1 .…”

Section: Biosynthesis Of Phamentioning

confidence: 99%

A Polyhydroxyalkanoates-Based Carrier Platform of Bioactive Substances for Therapeutic Applications

Zhang

Liu

Hao

et al. 2022

Front. Bioeng. Biotechnol.

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Bioactive substances (BAS), such as small molecule drugs, proteins, RNA, cells, etc., play a vital role in many therapeutic applications, especially in tissue repair and regeneration. However, the therapeutic effect is still a challenge due to the uncontrollable release and instable physico-chemical properties of bioactive components. To address this, many biodegradable carrier systems of micro-nano structures have been rapidly developed based on different biocompatible polymers including polyhydroxyalkanoates (PHA), the microbial synthesized polyesters, to provide load protection and controlled-release of BAS. We herein highlight the developments of PHA-based carrier systems in recent therapeutic studies, and give an overview of its prospective applications in various disease treatments. Specifically, the biosynthesis and material properties of diverse PHA polymers, designs and fabrication of micro- and nano-structure PHA particles, as well as therapeutic studies based on PHA particles, are summarized to give a comprehensive landscape of PHA-based BAS carriers and applications thereof. Moreover, recent efforts focusing on novel-type BAS nano-carriers, the functionalized self-assembled PHA granules in vivo, was discussed in this review, proposing the underlying innovations of designs and fabrications of PHA-based BAS carriers powered by synthetic biology. This review outlines a promising and applicable BAS carrier platform of novelty based on PHA particles for different medical uses.

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Section: Biosynthesis Of Phamentioning

confidence: 99%

A Polyhydroxyalkanoates-Based Carrier Platform of Bioactive Substances for Therapeutic Applications

Zhang

Liu

Hao

et al. 2022

Front. Bioeng. Biotechnol.

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“…Polyhydroxybutyrate (PHB), the most common member of the polyhydroxyalkanoates (PHAs), has been synthesized using multiple microorganisms and has been identified as a biodegradable polymer [ 22 , 23 , 24 ]. In a PHB metabolic pathway, acetyl-CoA is a key precursor in PHB production [ 25 ].…”

Section: Introductionmentioning

confidence: 99%

Development of Optogenetic Dual-Switch System for Rewiring Metabolic Flux for Polyhydroxybutyrate Production

et al. 2022

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Several strategies, including inducer addition and biosensor use, have been developed for dynamical regulation. However, the toxicity, cost, and inflexibility of existing strategies have created a demand for superior technology. In this study, we designed an optogenetic dual-switch system and applied it to increase polyhydroxybutyrate (PHB) production. First, an optimized chromatic acclimation sensor/regulator (RBS10–CcaS#10–CcaR) system (comprising an optimized ribosomal binding site (RBS), light sensory protein CcaS, and response regulator CcaR) was selected for a wide sensing range of approximately 10-fold between green-light activation and red-light repression. The RBS10–CcaS#10–CcaR system was combined with a blue light-activated YF1–FixJ–PhlF system (containing histidine kinase YF1, response regulator FixJ, and repressor PhlF) engineered with reduced crosstalk. Finally, the optogenetic dual-switch system was used to rewire the metabolic flux for PHB production by regulating the sequences and intervals of the citrate synthase gene (gltA) and PHB synthesis gene (phbCAB) expression. Consequently, the strain RBS34, which has high gltA expression and a time lag of 3 h, achieved the highest PHB content of 16.6 wt%, which was approximately 3-fold that of F34 (expressed at 0 h). The results indicate that the optogenetic dual-switch system was verified as a practical and convenient tool for increasing PHB production.

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“…Process optimization and metabolic engineering strategies have facilitated a deeper understanding of PHB production by recombinant E. coli from renewable carbon sources. However, the high costs of fermentation substrates and the remarkable energy consumption during the fermentation processes had impeded the application of PHB as a bio-based plastic [ 18 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

Biosynthesis of Poly-(3-hydroxybutyrate) under the Control of an Anaerobically Induced Promoter by Recombinant Escherichia coli from Sucrose

Zhou

Pei

et al. 2022

Molecules

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Poly-(3-hydroxybutyrate) (PHB) is a polyester with biodegradable and biocompatible characteristics and has many potential applications. To reduce the raw material costs and microbial energy consumption during PHB production, cheaper carbon sources such as sucrose were evaluated for the synthesis of PHB under anaerobic conditions. In this study, metabolic network analysis was conducted to construct an optimized pathway for PHB production using sucrose as the sole carbon source and to guide the gene knockout to reduce the generation of mixed acid byproducts. The plasmid pMCS-sacC was constructed to utilize sucrose as a sole carbon source, and the cascaded promoter P3nirB was used to enhance PHB synthesis under anaerobic conditions. The mixed acid fermentation pathway was knocked out in Escherichia coli S17-1 to reduce the synthesis of byproducts. As a result, PHB yield was improved to 80% in 6.21 g/L cell dry weight by the resulted recombinant Escherichia coli in a 5 L bed fermentation, using sucrose as the sole carbon source under anaerobic conditions. As a result, the production costs of PHB will be significantly reduced.

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Grand Challenges for Industrializing Polyhydroxyalkanoates (PHAs)

Cited by 191 publications

References 82 publications

A Polyhydroxyalkanoates-Based Carrier Platform of Bioactive Substances for Therapeutic Applications

A Polyhydroxyalkanoates-Based Carrier Platform of Bioactive Substances for Therapeutic Applications

Development of Optogenetic Dual-Switch System for Rewiring Metabolic Flux for Polyhydroxybutyrate Production

Biosynthesis of Poly-(3-hydroxybutyrate) under the Control of an Anaerobically Induced Promoter by Recombinant Escherichia coli from Sucrose

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