Potential and Prospects of Continuous Polyhydroxyalkanoate (PHA) Production
Abstract
:1. Introduction
Risk/Challenge | Remedy |
---|---|
Typically mesophile organisms are implemented in large-scale biotechnological production processes. Continuous cultivation of such organisms implies a substantial risk of microbial contamination; this can endanger whole fermentation batches, and, consequently, causes extensive economic loss. | Careful handling! High operational skills of staff! Application of extremophile production strains (e.g., thermophiles, osmophiles), which are robust, and outperform the growth rate of microbial competitors! Continuous antibiotic feed (generally not recommended!) |
Long-term stability of production strain not assured | Strain improvement by genetic engineering. Application of robust production strains, which are rigid enough to withstand the shear forces generated by peristaltic pumping. Application of microbial fermentation broth that can conveniently be pumped (impedes the application of mycelia-forming species!) |
Coming from the bioreactor’s interior, microbes may reach the tank of sterile medium; by subsequent conversion of substrate compounds, this can change the feed composition | Taking appropriate technical precautions, such as interrupting the liquid path in tubes by air barriers in which the medium drops, or by implementing thermo-traps (heating of the medium), etc. Note: Medium quality needs to be verified after the thermo-trap: precipitation or destruction of heat labile components has to be avoided. |
Dropping of the media into the bioreactor’s interior (cultivation broth) results in small nutrient pulses and thus locally inconsistent nutrient concentrations. The same goes for locally fluctuating pH-values by acid or hydroxide pulses to maintain the pH-value. This prevents real “steady state” conditions. | Reduction of the volume ratio droplets/fermentation broth (small droplets favorable) |
Highly fragile microbial cells can get disrupted by agitation and aeration | If possible, no excessive agitation and aeration. Application of robust microbial strains. Application of special stirrer (impeller) systems, which generate less shear stress. |
Cell growth on the inner walls or other surfaces (e.g., baffles, probes, etc.) of the bioreactor during long-term operation | Equipping the reactor wall with a hydrophobic surface by application of e.g., silanes. “Close clearance” of inner walls by stirrers operating close to the wall |
If mixing does not occur completely uniform, true “steady state” conditions are not warranted | Application of advanced adapted mixing systems (encompasses stirrer, sparger, baffles) |
Instable reactor volumes by foaming, resulting in an overflow of fermentation broth | Application of effective antifoam agents tailored for the substrate-strain combination. Mechanical foam suppression by “anti-foam centrifuge”. Integrated solution: Application of a mass controlled pump (“mass-stat regime”) in combination with foam sensors and antifoam solutions. |
Process separated in different phases (formation of secondary bio-product PHA after autocatalytic phase of biomass formation): optimum composition of the feed stream varies for the two different phases | Switch from single- to multistage continuous processes |
2. Continuous vs. Discontinuous PHA Production
Criterion | Benefit | References |
---|---|---|
Investment costs for bioreactor | Due to higher volumetric productivity in continuous processes, (fed)batch cultivation requires large bioreactor facilities to generate the same output per time; continuous production contributes to lower investment costs by resorting to smaller operation facilities | [32] |
Time demand | No “dead time” needed for pre- and post-treatment (“re-vamping”) of bioreactor | [32] |
Investment costs for downstream processing | Manageable quantities of PHA-rich biomass accrue continuously. Downstream processing (e.g., extraction) of crude product stream can be accomplished continuously in smaller (cheaper!) recovery facilities. | [32,42] |
Labor intensity | Higher for (fed)batch processes; not too much effort needed from staff during continuous operation as soon as steady-state conditions are reached. | [32] |
Product quality | Higher consistency and uniformity of product quality (molar mass distribution, distribution of monomeric building blocks, thermal properties) | [43,44,45,46] |
Triggering of polyester composition | Easier in continuous processes by possibility to exactly trigger the ratio between main- and co-substrates in the continuous feed stream. In multi-stage continuous processes: Possibility to design blocky structured polyesters consisting of soft- and hard segments. | [43,44,46,47,48] |
Triggering molar masses | The applied dilution rate D significantly impacts the molar mass of PHA (molar mass direct proportional to D) | [49] |
Making toxic substrates better accessible to the production strain | Toxic substrates can be continuously supplied exactly in accordance to their conversion by the cells. Thus, inhibiting concentration are never reached, actual zero concentration in cultivation medium. In addition, one can even profit from dual nutrient limited (DNL) growth conditions. Note: The acceptable substrate concentration depends on the strain properties (substrate affinity, Ks) and the specific growth rate µ (or D at steady-state, respectively) at which the strain is cultured. Excessively increasing D can cause a wash-out of the culture because of the increased substrate toxicity which by itself reduces the specific growth rate! | [33,43,44,50,51] |
Convenient method for medium development and optimization | Fast reaction of steady-state culture kinetics to changing process parameters such as substrate concentrations triggered by pulse, shift or transient changes, temperature, pH-value, etc. | [41,52] |
Year | Strain | Aim | PHA Produced | Significance of the Work for the Scientific Field | Reference |
---|---|---|---|---|---|
1972 | Azotobacter beijerinkii NCIB 9067 | Investigating the impact of oxygen limitation on PHA synthesis | PHB | First reported continuous PHA production | [53] |
1986 | Hyphomicrobium ZV620 | Investigating the impact of carbon to nitrogen ratio and D on activity of NH4+-assimilating enzymes, and on cellular composition (PHB content in biomass) | PHB | Confirmation of significance of carbon to nitrogen ratio to PHA mass fraction in biomass, confirmation of impact of D on cellular composition | [54] |
1990 | Cupriavidus necator DSM 545 | Increase of PHA productivity and intracellular PHA fraction by continuous operation | PHBHV | First continuous PHA production to enhance product output First continuous copolyester production | [47] |
1990 | Haloferax mediterranei DSM 1411 | Monoseptic continuous cultivation of osmophilic strain under unsterile conditions (“septic process”) for high-throughput PHA production | PHBHV | First continuous PHA production under unsterile conditions using extremophiles | [40] |
1991 | Ps. putida GPo1 | Continuous production of mcl-PHA from fatty acids and octane | mcl-PHA | First continuous mcl-PHA production | [52,55] |
1995 | Cupriavidus necator DSM 545 | Investigating the impact of D on polyester composition and productivity | PHBHV | First insights on impact of D on PHA production (quality and quantity) | [49] |
2000 | Ps. putida GPo1 | Continuous production of mcl-PHA from fatty acids under de facto C- and N-limitation | mcl-PHA | First Dual Nutrient Limited (DNL) continuous PHA production | [50] |
2005 | Cupriavidus necator DSM 545 | Continuous production of scl-PHA copolyesters with pre-determined monomeric composition | PHBHV | First triggering of scl-PHA copolyester composition on the nonomeric level by varying the composition of the continuous feed stream | [43] |
2004 | Ps. putida GPo1 | Continuous production of mcl-PHA copolyesters with pre-determined monomeric composition | mcl-PHA with aromatic building blocks | First triggering of mcl-PHA copolyester composition on the nonomeric level by varying the composition of the continuous feed stream First continuous production of an aromatic mcl-PHA | [56] |
2009 | Ps. putida GPo1 | Production of non-amorphous (crystalline) mcl-PHA on a relevant scale | mcl-PHA with aromatic building blocks | First continuous production of a crystalline mcl-PHA | [45] |
3. Single-Stage Continuous Systems with Pure Cultures
3.1. Scl-PHA Production by Single-Stage Continuous Cultures
3.2. Mcl-PHA Production by Single-Stage Continuous Cultures
4. Two-Stage Continuous Systems with Pure Cultures
4.1. Scl-PHA Production by Two-Stage Continuous Cultures
4.2. Mcl-PHA Production by Two-Stage Continuous Cultures
5. Multistage Process with Pure Cultures
6. Strategies for Continuous Enrichment of PHA-Accumulating Organisms
7. Unsterile and Open Continuous Processes for PHA Production
8. Conclusions
Acknowledgements
Author Contributions
Conflicts of Interest
References
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Koller, M.; Braunegg, G. Potential and Prospects of Continuous Polyhydroxyalkanoate (PHA) Production. Bioengineering 2015, 2, 94-121. https://doi.org/10.3390/bioengineering2020094
Koller M, Braunegg G. Potential and Prospects of Continuous Polyhydroxyalkanoate (PHA) Production. Bioengineering. 2015; 2(2):94-121. https://doi.org/10.3390/bioengineering2020094
Chicago/Turabian StyleKoller, Martin, and Gerhart Braunegg. 2015. "Potential and Prospects of Continuous Polyhydroxyalkanoate (PHA) Production" Bioengineering 2, no. 2: 94-121. https://doi.org/10.3390/bioengineering2020094