Presentation Information
[2BRBP-10]Industrial Scale-Up of D-β-Hydroxybutyrate (D-BHB) Production Using Halomonas sp. KM-1: A Tens-of-Kiloliter Case Study in Japan
○Jun TSUBOTA1, Atsushi KOBAYASHI1, yoshikazu KAWATA1, Shohei KATSUYA1 (1. Osaka Gas co., ltd. (Japan))
Keywords:
bio-manufacturing,D-BHB,Industrial Scale-up
[Purpose] The objective of this study is to establish and validate the industrial-scale fermentation conditions for D-β-hydroxybutyrate (D-BHB) using the halophilic bacterium Halomonas sp. KM-1. While laboratory-scale success has been documented, transitioning to a scale of several tens of kiloliters (kL) is essential for commercial viability in Japan’s bio-manufacturing sector. This research focuses on synchronizing metabolic switching and oxygen transfer efficiency across vastly different reactor volumes.
[Method]Halomonas sp. KM-1 exhibits a unique biphasic metabolism: it accumulates intracellular polyhydroxybutyrate (PHB) under aerobic conditions and subsequently degrades PHB to excrete D-BHB extracellularly under anaerobic conditions.Using sucrose as the primary carbon source, we designed a transition strategy based on laboratory-scale (3L) fermentation parameters. The scaling strategy prioritized the Oxygen Transfer Rate (OTR) and Volumetric Oxygen Transfer Coefficient (kLa) during the growth/accumulation phase, and precise redox potential control during the excretion phase. Key operational factors, including agitation tip speed and aeration profiles, were adjusted to compensate for the increased hydrostatic pressure and mixing lag inherent in large-scale fermenters.
[Results]Despite the physical differences in fermenter geometry and gas dispersion at the tens-kL scale, the fermentation conditions were successfully synchronized by optimizing a limited set of operational variables.Production Yield: The industrial-scale test successfully achieved a D-BHB concentration of 120 g/L within 70 hours.Consistency: The production kinetics at the tens-kL scale showed an excellent correlation with laboratory-scale data, demonstrating the high robustness of the KM-1 strain against mechanical shear stress and large-scale environmental gradients.
[Consideration]The results indicate that the metabolic flux of Halomonas sp. KM-1 is highly scalable. The extension in fermentation time (compared to lab scale) was successfully mitigated by optimizing fermentation conditions, ensuring that industrial productivity remains economically competitive.
[Conclusion]We have successfully fixed the commercial production parameters for D-BHB using a tens-kL scale fermenter. This achievement positions Halomonas sp. KM-1 as a formidable bio-manufacturing platform. We are currently expanding this platform to produce a variety of materials. The establishment of this large-scale fermentation technology provides a robust foundation for new bio-business ventures and contributes to the realization of a sustainable, microbial-based chemical industry.
[Method]Halomonas sp. KM-1 exhibits a unique biphasic metabolism: it accumulates intracellular polyhydroxybutyrate (PHB) under aerobic conditions and subsequently degrades PHB to excrete D-BHB extracellularly under anaerobic conditions.Using sucrose as the primary carbon source, we designed a transition strategy based on laboratory-scale (3L) fermentation parameters. The scaling strategy prioritized the Oxygen Transfer Rate (OTR) and Volumetric Oxygen Transfer Coefficient (kLa) during the growth/accumulation phase, and precise redox potential control during the excretion phase. Key operational factors, including agitation tip speed and aeration profiles, were adjusted to compensate for the increased hydrostatic pressure and mixing lag inherent in large-scale fermenters.
[Results]Despite the physical differences in fermenter geometry and gas dispersion at the tens-kL scale, the fermentation conditions were successfully synchronized by optimizing a limited set of operational variables.Production Yield: The industrial-scale test successfully achieved a D-BHB concentration of 120 g/L within 70 hours.Consistency: The production kinetics at the tens-kL scale showed an excellent correlation with laboratory-scale data, demonstrating the high robustness of the KM-1 strain against mechanical shear stress and large-scale environmental gradients.
[Consideration]The results indicate that the metabolic flux of Halomonas sp. KM-1 is highly scalable. The extension in fermentation time (compared to lab scale) was successfully mitigated by optimizing fermentation conditions, ensuring that industrial productivity remains economically competitive.
[Conclusion]We have successfully fixed the commercial production parameters for D-BHB using a tens-kL scale fermenter. This achievement positions Halomonas sp. KM-1 as a formidable bio-manufacturing platform. We are currently expanding this platform to produce a variety of materials. The establishment of this large-scale fermentation technology provides a robust foundation for new bio-business ventures and contributes to the realization of a sustainable, microbial-based chemical industry.
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