Commercial Generic Bioprocessing Apparatus - Antibiotic Production in Space (CGBA-APS) - 05.13.15
Previous studies showed increased antibiotic production during short duration space flights. The CGBA-APS investigation examined actinomycin D production, an antibiotic, during long term exposure to microgravity to determine the mechanism that caused the increased antibiotic production. Once the mechanism is determined, it can be applied to Earth based pharmaceutical manufacturing techniques. Science Results for Everyone
The good news: antibiotics grow faster in space. The bad news: scientists aren’t sure how. The bacteria Streptomyces plicatus was used to produce an antibiotic, actinomycin D, on the International Space Station. Initial production was higher than that on the ground, an increase also seen on day 8 and day 12. However, day 16 and on, the ground experiment produced more antibiotics than that in space. Causes for initial higher yield are unknown, but one theory is that a shorter lag phase allowed the ISS samples to reach growth and production phases sooner. Identifying the mechanism involved and transferring it to Earth-based production could enhance our drug supply. Experiment Details
David M. Klaus, Ph.D., BioServe Space Technologies, Boulder, CO, United States
Ray Lam, Ph.D., Nereus Pharmaceuticals, Incorporated, San Diego, CA, United States
BioServe Space Technologies, University of Colorado, Boulder, CO, United States
Sponsoring Space Agency
National Aeronautics and Space Administration (NASA)
Human Exploration and Operations Mission Directorate (HEOMD)
ISS Expedition Duration
March 2001 - June 2002
Previous ISS Missions
CGBA investigations have been performed on STS-77, STS-80 and STS-95. The first CGBA investigation was performed during Increment 0.
- Space flight pharmaceutical research introduced the potential to obtain unique insight into the natural production of antibiotic processes in microbial organisms in the absence of gravity.
- The purpose of this investigation was to increase the absolute yield of antibiotic (actinomycin D) production by Streptomyces plicatus for an extended duration of time in microgravity.
- This investigation helps lay the foundation for future commercialization of pharmaceutical production utilizing microgravity.
The objective of this experiment was to determine if secondary metabolite production in microbes was impacted by long-duration space flight. Previous research, conducted during short-duration Space Shuttle flights, identified significant potential for antibiotic production by microorganisms in orbit. The CGBA-Antibiotic Production in Space (APS) experiment was the first ISS investigation to test whether long-duration exposure to microgravity stimulated antibiotic production in microorganisms. CGBA-APS spent at total of 72 days in orbit on ISS. The experiment used Streptomyces plicatus to produce the antibiotic compound actinomycin D. Actinomycin D is an anti-tumor antibiotic used to treat tumors of the bone, urogential tract, skeletal muscle, kidney, and testis.
The Commercial Generic Bioprocessing Apparatus (CGBA) provided automated processing for biological experiments. For CGBA-APS, the CGBA hardware included the isothermal containment module (ICM v.3) The ICM v.3 contained the Multiple Orbital Bioreactor with Instrumentation and Automated Sampling (MOBIAS), a fermentation, cell culture, and tissue engineering apparatus.
The ICM v.3 provided highly-accurate temperature control between 4 degrees C and 37 degrees C and was equipped with data, video, and telemetry electronics to allow telescience remote operation. The ICM held six stackable MOBIAS trays, each of which provided the appropriate controlled, sterile sample processing environment, with passive gas exchange and automated sampling and waste removal. The samples that were fermented were kept in 5 ml teflon bags and processed in separate culture bags. Waste and media, to feed the experiments, were contained in 350 ml bags. Each tray contained its own array of sample, culture, media, waste bags, and connectors. The CGBA provided independent, adjustable temperature control for both the sample and culture bags.
Bacteria produce antibiotics at an accelerated rate in microgravity when compared to those that are produced on Earth. The ability to grow large quantities of antibiotics in microgravity will further pharmaceutical research.
Scientists will apply the insight gained from observations made in the microgravity environment of space towards improving antibiotic production and efficiency in facilities on Earth. The economic gain would be substantial in a small increase in fermentation efficiency, realized as a result of the knowledge gained from the space flight data. The microgravity environment is essential in determining the critical factors observed in increasing an antibiotic production.
CGBA-APS required continuous power which was provided through an EXPRESS Rack. A total of 42 culture samples were used in this investigation. The ICM required minimal crew time and the MOBIAS was fully automated. The Remote Payload Operations Center (R-POCC) at the University of Colorado monitored the downlinked data and sent commands directly to the EXPRESS Rack.
The culture samples were loaded in the CGBA assembly preflight and launched on the Space Shuttle. Once the equipment was transferred to ISS, the crewmembers installed the CGBA hardware into an EXPRESS Rack. From this point, the investigation is automated and the crew performed only the required daily hardware health checks and weekly cleaning.
The cultures were kept at a temperature of 10 degrees C for the first 21 days of the mission. To initiate growth, the temperature was increased to 22 degrees C by the ground-based science team and monitored from the BioServe Remote Payload Operations Control Center in Boulder, CO, via video and data downlink. The samples that produced actinomycin D were stored in a thermally isolated portion of the locker at 4 degrees C for analysis by the ground teams following return to Earth.
CGBA-APS originally flew on Expedition 2 but was not able to function due to technical issues. Its re-flight took place during Expedition 4 where the hardware performed as planned. Samples of antibiotic were taken at four-day intervals. A total of 48 samples of Streptomyces plicatus were used to produce the antibiotic compound actinomycin D for a span of 72 days on orbit. The initial production of actinomycin D from on-orbit samples was higher than those produced during the ground tests. This was true for samples that were taken on day 8 (15.6 % increase) and day 12 (28.5% increase) of the investigation. Beginning at day 16, the ground experiment produced more antibiotic than the on-orbit experiment. This trend continued for the remainder of the experiment. The causes for the higher yield during the first 12 days of the experiment are still unknown. One theory is that there is a shorter lag phase, which allowed ISS samples to reach the growth and production phases sooner than the ground samples (Benoit et al. 2005).
Identifying the mechanism that caused increased production of antibiotics while in microgravity and applying them to production on Earth could be advantageous to the pharmaceutical industry. A method for transferring the microgravity research results to Earth-based production has not yet been identified. (Evans et al. 2009)
Benoit MR, Li W, Stodieck LS, Lam KS, Winther CL, Roane TM, Klaus DM. Microbial Antibiotic Production Aboard the International Space Station. Applied Microbiology and Biotechnology. 2006; 70(4): 403-411. DOI: 10.1007/s00253-005-0098-3.
Ground Based Results Publications
Klaus DM, Howard HN. Antibiotic efficacy and microbial virulence during space flight. Trends in Biotechnology. 2006 Mar; 24(3). DOI: 10.1016/j.tibtech.2006.01.008.
Lam KS, Gustavson DR, Pirnik DL, Pack E, Bulanhagui C, Mamber SW, Forenza S, Stodieck LS, Klaus DM. The effect of space flight on the production of actinomycin D by Streptomyces plicatus. Journal of Industrial Microbiology and Biotechnology. 2002; 29(6): 299-302.
Klaus DM. Gravitational Influence on Biomolecular Engineering Processes. Gravitational and Space Biology. 2004; 17: 51-65.
Lam KS, Mamber SW, Pack E, Forenza S, Fernandes PB, Klaus DM. The Effects of Space Flight on the Production of Monorden by Humicola fuscoatra WC5157 in Solid State Fermentation. Applied Microbiology and Biotechnology. 1998; 49(5): 579-583.
Klaus DM, Benoit MR, Bonomo M, Bollich J, Freeman J, Stodieck LS, McClure G, Lam KS. Antibiotic Production in Space using an Automated Fed-Bioreactor System. Conference and Exhibit on International Space Station Utilization, Cape Canaveral, FL; 2001 2001-4921.
Chynoweth DP, Owens JM, Teixeira AA, Pullammanappallil P, Luniya SS. Anaerobic Digestion of Space Mission Wastes. Water Science and technology: A Journal of the International Association on Water Pollution Research. 2006; 53: 177-186.
Matin A, Lynch SV, Benoit MR. Increased Bacterial Resistance and Virulence in Simulated Microgravity and its Molecular Basis. Gravitational and Space Biology. 2006; 19: 31-42.
Klaus DM, Brown R, Cierpik K. Antibiotic Production in Space. American Institute of Physics Conference Proceedings. 1998; 420: 633-637. DOI: 10.1063/1.54857.
Klaus DM. Microgravity and its Implication for Fermentation Biotechnology. Trends in Biotechnology. 1998; 16(9): 369-373. DOI: 10.1016/S0167-7799(98)01197-4.
Science @ NASA
A Modular Suite of Hardware Enabling Space Flight Cell Culture Research - Commercial Generic Bioprocessing Apparatus (CGBA)
BioServe Space Technologies
NASA Fact Sheet
NASA Image: ISS004E11048 - CGBA Isothermal Containment Module (ICM) v.3, installed in EXPRESS just above astronaut Dan Bursch's extended left arm.
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Post flight images show MOBIAS tray with waste bag and samples visible (dark substance indicates actinomycin D), close up of remaining viable culture from opened tray, and sample bags. Courtesy image of Marshall Space Center.
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"Helping to develop and operate the MOBIAS payload provided me with an excellent opportunity to combine my background in microbiology with the engineering skills I learned while at BioServe. A substantial portion of my Ph.D. dissertation was devoted to this project, and this multidisciplinary experience helped me obtain my current position as a Post-Doctoral Scholar at Stanford University." Mike Benoit, PhD.
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