Pilot Scale‐up of Poly(3‐hydroxybutyrate‐<i>co</i>‐4‐hydroxybutyrate) Production by <i>Halomonas bluephagenesis</i> via Cell Growth Adapted Optimization Process

Ye, Jianwen; Huang, Weifeng; Wang, Dongsheng; Chen, Fengyi; Yin, Jun; Li, Teng; Zhang, Haoqian

doi:10.1002/biot.201800074

Cited by 66 publications

(46 citation statements)

References 29 publications

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“…In pilot-scale (1000 L), 61 wt% of P(3HB-co-16 mol% 4HB) were accumulated in the cells with a productivity of 1.04 g L −1 h −1 . In a follow up publication (Ye et al, 2018b), H. bluephagenesis TD01 was further modified by the deletion of its succinate semialdehyde dehydrogenase gene (gabD) resulting in the strain TD40 (Figure 2). Glucose, γ-butyrolactone, and waste corn steep liquor were used as carbon sources for growth and polymer production.…”

Section: Recombinant Strains For the Synthesis Of P4hb Homopolymer Anmentioning

confidence: 99%

Poly(4-Hydroxybutyrate): Current State and Perspectives

Utsunomia

Ren

Zinn

2020

Front. Bioeng. Biotechnol.

107

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By the end of 1980s, for the first time polyhydroxyalkanoate (PHA) copolymers with incorporated 4-hydroxybutyrate (4HB) units were produced in the bacterium Cupriavidus necator (formally Ralstonia eutropha) from structurally related carbon sources. After that, production of PHA copolymers composed of 3-hydroxybutyrate (3HB) and 4HB [P(3HB-co-4HB)] was demonstrated in diverse wild-type bacteria. The P4HB homopolymer, however, was hardly synthesized because existing bacterial metabolism on 4HB precursors also generate and incorporate 3HB. The resulting material assumes the properties of thermoplastics and elastomers depending on the 4HB fraction in the copolyester. Given the fact that P4HB is biodegradable and yield 4HB, which is a normal compound in the human body and proven to be biocompatible, P4HB has become a prospective material for medical applications, which is the only FDA approved PHA for medical applications since 2007. Different from other materials used in similar applications, high molecular weight P4HB cannot be produced via chemical synthesis. Thus, aiming at the commercial production of this type of PHA, genetic engineering was extensively applied resulting in various production strains, with the ability to convert unrelated carbon sources (e.g., sugars) to 4HB, and capable of producing homopolymeric P4HB. In 2001, Metabolix Inc. filed a patent concerning genetically modified and stable organisms, e.g., Escherichia coli, producing P4HB and copolymers from inexpensive carbon sources. The patent is currently hold by Tepha Inc., the only worldwide producer of commercial P4HB. To date, numerous patents on various applications of P4HB in the medical field have been filed. This review will comprehensively cover the historical evolution and the most recent publications on P4HB biosynthesis, material properties, and industrial and medical applications. Finally, perspectives for the research and commercialization of P4HB will be presented.

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Section: Recombinant Strains For the Synthesis Of P4hb Homopolymer Anmentioning

confidence: 99%

Poly(4-Hydroxybutyrate): Current State and Perspectives

Utsunomia

Ren

Zinn

2020

Front. Bioeng. Biotechnol.

107

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“…So far NGIB has been only successfully conducted based on Halomonas spp. grown in seawater or NaCl containing culture (Ye, Hu, et al, 2018;Ye, Huang, et al, 2018).…”

Section: Enhanced Phb Synthesis By Overexpressing Heterologous Phacmentioning

confidence: 99%

Engineering self‐flocculating Halomonas campaniensis for wastewaterless open and continuous fermentation

Chen

Qiao

Shuai

et al. 2019

Biotech & Bioengineering

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Halomonas has been developed as a platform for the next generation industrial biotechnology allowing open and nonsterile growth without microbial contamination under a high-salt concentration and alkali pH. To reduce downstream cost associated with continuous centrifugation and salt containing wastewater treatment, Halomonas campaniensis strain LS21 was engineered to become self-flocculating by knocking out an etf operon encoding two subunits of an electron transferring flavoprotein in the predicted electron transfer chain. Self-flocculation could be attributed to the decrease of the surface charge and increase of the cellular hydrophobicity resulted from deleted etf. A wastewaterless fermentation strategy based on the self-flocculating H. campaniensis was developed for growth and the production of poly-3-hydroxybutyrate (PHB) as an example. Most microbial cells flocculated and precipitated to the bottom of the bioreactor within 1 min after stopping the aeration and agitation. The supernatant can be used again without sterilization or inoculation for the growth of the next batch after collecting the precipitated cell mass. The wastewaterless process was conducted for four runs without generating wastewater. PHB accumulation by the self-flocculent strain was enhanced via promoter and ribosome binding site optimizations, the productivities of cell dry weight and PHB were increased from 0.45 and 0.18 g·L −1 ·hr −1 for the batch process compared to 0.82 and 0.33 g·L −1 ·hr −1 for the wastewaterless continuous process, respectively. This has clearly demonstrated the advantages of the wastewaterless process in that it not only reduces wastewater but also increases cell growth and product formation efficiency in a given period of time. K E Y W O R D S continuous process, etf, flocculation, Halomonas campaniensis, next generation industry biotechnology, NGIB, PHB

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“…Compared to PHB and PHBV, 4HB-containing PHA has a wide variety of mechanical and physical properties. Depending on the 4HB content, polymer property changes from crystallinity to elasticity [124]. 4HB incorporation not only widens the application potentials but also improves the biodegradability of PHA [125].…”

Section: Synthesis Of Pha Containing 4-hydroxybutyrate (4hb) Monomermentioning

confidence: 99%

“…When scaled up to 1000-L fermentor vessel, 82.6 g/L CDW containing 61% (wt) P(3HB-co-16 mol% 4HB) was achieved after 48 h. The produced P3HB4HB was a block copolymer and thus exhibited good elasticity with an elongation at break of 1022 ± 43%. Furthermore, the recombinant strain efficiently gave 81.4 g/ L CDW containing 73.8% (wt) P(3HB-co-11.6 mol% 4HB) in 7.5-L fermentor when waste corn steep liquor (CSL) along with glucose and GBL was used as substrates [124]. Further scale up to 5000-L fermentor generated 99.6 g/L CDW containing 60.4% (wt) P(3HB-co-13.5 mol% 4HB).…”

Section: Synthesis Of Pha Containing 4-hydroxybutyrate (4hb) Monomermentioning

confidence: 99%

Current developments on polyhydroxyalkanoates synthesis by using halophiles as a promising cell factory

et al. 2020

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Plastic pollution is a severe threat to our environment which necessitates implementation of bioplastics to realize sustainable development for a green world. Polyhydroxyalkanoates (PHA) represent one of the potential candidates for these bioplastics. However, a major challenge faced by PHA is the high production cost which limits its commercial application. Halophiles are considered to be a promising cell factory for PHA synthesis due to its several unique characteristics including high salinity requirement preventing microbial contamination, high intracellular osmotic pressure allowing easy cell lysis for PHA recovery, and capability to utilize wide spectrum of low-cost substrates. Optimization of fermentation parameters has made it plausible to achieve large-scale production at low cost by using halophiles. Further deeper insights into halophiles have revealed the existence of diversified and even novel PHA synthetic pathways within different halophilic species that greatly affects PHA type. Thus, precise metabolic engineering of halophiles with the help of advanced tools and strategies have led to more efficient microbial cell factory for PHA production. This review is an endeavour to summarize the various research achievements in these areas which will help the readers to understand the current developments as well as the future efforts in PHA research.

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Pilot Scale‐up of Poly(3‐hydroxybutyrate‐co‐4‐hydroxybutyrate) Production by Halomonas bluephagenesis via Cell Growth Adapted Optimization Process

Cited by 66 publications

References 29 publications

Poly(4-Hydroxybutyrate): Current State and Perspectives

Poly(4-Hydroxybutyrate): Current State and Perspectives

Engineering self‐flocculating Halomonas campaniensis for wastewaterless open and continuous fermentation

Current developments on polyhydroxyalkanoates synthesis by using halophiles as a promising cell factory

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