Abstract
Previous studies examining metabolic characteristics of bacterial cultures have mostly suggested that reduced gravity is advantageous for microbial growth. As a consequence, the question of whether space flight would similarly enhance secondary metabolite production was raised. Results from three prior space shuttle experiments indicated that antibiotic production was stimulated in space for two different microbial systems, albeit under suboptimal growth conditions. The goal of this latest experiment was to determine whether the enhanced productivity would also occur with better growth conditions and over longer durations of weightlessness. Microbial antibiotic production was examined onboard the International Space Station during the 72-day 8A increment. Findings of increased productivity of actinomycin D by Streptomyces plicatus in space corroborated with previous findings for the early sample points (days 8 and 12); however, the flight production levels were lower than the matched ground control samples for the remainder of the mission. The overall goal of this research program is to elucidate the specific mechanisms responsible for the initial stimulation of productivity in space and translate this knowledge into methods for improving efficiency of commercial production facilities on Earth.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Brown RB, Klaus D, Todd P (2002) Effects of space flight, clinorotation, and centrifugation on the substrate utilization efficiency of E. coli. Microgravity Sci Technol XIII:24–29
Ciferri O, Tiboni O, Dipasquale G, Orlandoni AM, Marchesi ML (1986) Effects of microgravity on genetic recombination in Escherichia coli. Naturwissenschaften 73:418–421
Demain A (1999) Pharmaceutically active secondary metabolites of microorganisms. Appl Microbiol Biotechnol 52:455–463
Demain AL, Fang A (2001) Secondary metabolism in simulated microgravity. Chem Rec 1:333–346
DeVuyst L, Callewaert R, Crabbe K (1996) Primary metabolite kinetics of bacteriocin biosynthesis by Lactobacillus amylovorus and evidence for stimulation of bacteriocin production under unfavourable growth conditions. Microbiology 142:817–827
Doull JL, Singh AK, Hoare M, Ayer SW (1994) Conditions for the production of jadomycin B by Streptomyces venezuelae ISP5230: effects of heat shock, ethanol treatment and phage infection. J Ind Microbiol 13:120–125
Fang A, Pierson DL, Mishra SK, Koenig DW, Demain AL (1997a) Secondary metabolism in simulated microgravity: β-lactam production by Streptomyces clavuligerus. J Ind Microbiol Biotech 24:22–25
Fang A, Pierson DL, Mishra SK, Koenig DW, Demain AL (1997b) Effect of simulated microgravity and shear stress on microcin B17 production by Escherichia coli and its excretion into the medium. Appl Environ Microbiol 63:4090–4092
Fang A, Pierson DL, Mishra SK, Koenig DW, Demain AL (1997c) Gramicidin S production by Bacillus brevis in simulated microgravity. Curr Microbiol 34:119–204
Fang A, Pierson DL, Mishra SK, Demain AL (2000) Growth of Streptomyces hygroscopicus in rotating-wall bioreactor under simulated microgravity inhibits rapamycin production. Appl Microbiol Biotechnol 54:33–36
Gao Q, Fang A, Pierson DL, Mishra SK, Demain AL (2001) Shear stress enhances microcin B17 production in a rotating wall bioreactor, but ethanol stress does not. Appl Microbiol Biotechnol 56:384–387
Gasset G, Tixador R, Eche B, Lapchine L, Moatti N, Toorop P, Woldringh C (1994) Growth and division of Escherichia-Coli under microgravity conditions. Res Microbiol 145:111–120
Hardisson C, Manzanal M-B, Salas J-A, Suárez J-E (1978) Fine structure, physiology and biochemistry of arthrospore germination in Streptomyces antibioticus. J Gen Microbiol 105:203–214
Hege-Treskatis D, King R, Wolf H, Gilles ED (1992) Nutritional control of nikkomycin and juglomycin production by Streptomyces tendae in continuous culture. Appl Microbiol Biotechnol 36:440–445
Hoehn A, Klaus D, Stodieck L (2004) A modular suite of hardware enabling space flight cell culture research. J Gravit Physiol 11(1):39–50
James PDA, Edwards C, Dawson M (1991) The effects of temperature, pH and growth-rate on secondary metabolism in Streptomyces-Thermoviolaceus grown in a chemostat. J Gen Microbiol 137:1715–1720
Kacena M, Todd P (1997) Growth characteristics of E-coli and B-subtilis cultured on an agar substrate in microgravity. Microgravity Sci Technol 10:58–62
Kacena MA, Merrell GA, Manfredi B, Smith EE, Klaus DM, Todd P (1999) Bacterial growth in space flight: logistic growth curve parameters for Escherichia coli and Bacillus subtilis. Appl Microbiol Biotechnol 51:229–234
Klaus DM (1998) Microgravity and its implication for fermentation technology. Trends Biotechnol 16(9):369–373
Klaus DM (2002) Space microbiology: microgravity and microorganisms. In: Britton G (ed) The encyclopedia of environmental microbiology. Wiley, NY, pp 2996–3004
Klaus DM (2004) Gravitational influence on biomolecular engineering processes. Gravit Space Biol Bull 17:51–65
Klaus D, Simske S, Todd P, Stodieck L (1997) Investigation of space flight effects on Escherichia coli and a proposed model of underlying physical mechanisms. Microbiology 143:449–455
Klaus D, Benoit M, Bonomo J, Bollich J, Freeman J, Stodieck L, McClure G, Lam KS (2001) Antibiotic production in space using an automated fed-bioreactor system. Proceedings of the AIAA conference on ISS utilization, AIAA 2001–4921
Klaus D, Benoit M, Nelson E, Hammond T (2004) Extracellular mass transport considerations for space flight research concerning suspended and adherent in vitro cell cultures. J Gravit Physiol 11(1):17–28
Lam KS, Mamber S, Pack E, Forenza S, Fernandes P, Klaus D (1998) The effects of space flight on the production of monorden by Humicola fuscoatra WC5157 in solid state fermentation. Appl Microbiol Biotechnol 49:579–583
Lam KS, Gustavson DR, Pirnik D, Pack E, Bulanhagui C, Mamber SW, Forenza S, Stodieck LS, Klaus DM (2002) The effect of space flight on the production of actinomycin D by Streptomyces plicatus. J Ind Microbiol Biotech 29:299–302
Lapchine I, Moatti N, Richoilley G, Templier J, Gasset G, Tixador R (1988) The antibio experiment. In: Biorack on Spacelab D-1, ESA SP-1091, pp 45–51
Mattoni RHT (1968) Space-flight effects and gamma radiation interaction on growth and induction of lysogenic bacteria. Bioscience 18:602–608
Mennigmann HD, Heise M (1994) Response of growing bacteria to reduction in gravity. Fifth European symposium on life sciences research in space, ESA-366, Arcachon, France, pp 83–87
Mennigmann HD, Lange M (1986) Growth and differentiation of Bacillus subtilis under microgravity. Naturwissenschaften 73:415–417
Mishra SK, Pierson DL (1992) Space flight, effects on microorganisms. In: Lederberg J (ed) Encyclopedia of microbiology, vol 4. Academic, San Diego, pp 53–60
Miyadoh S (1993) Research on antibiotic screening in Japan over the last decade: a producing microorganisms approach. Actinomycetologia 7:100–106
Montgomery POB, Cook JE, Reynolds RC, Paul JS, Hayflick L, Stock D, Schulz WW, Kimsey S, Thirolf RG, Rogers T, Cambell D (1978) The response of single human cells to zero gravity. In Vitro 14:165–173
Mortvedt-Abildgaard C, Nissen-Meyer J, Jelle B, Grenov B, Skaugen M, Nes I (1995) Production and pH-dependent bactericidal activity of lactocin S, a lantibiotic from Lactobacillus sake L45. Appl Environ Microbiol 61:175–179
Nakata K, Yoshimoto A, Yamada Y (1999) Promotion of antibiotic production by high ethanol, high NaCl concentration, or heat shock in Pseudomonas fluorescens S272. Biosci Biotechnol Biochem 63:293–297
Pirt SJ, Righelato RC (1967) Effect of growth rate on the synthesis of penicillin by Penicillium chrysogenum in batch and chemostat cultures. Appl Microbiol 15:1284–1290
Silver L, Bostian K (1990) Screening of natural products for antimicrobial agents. Eur J Clin Microbiol Infect Dis 9:455–461
Singh MP, Greenstein M (2000) Antibacterial leads from microbial natural products discovery. Curr Opin Drug Discov Dev 3:167–176
Thévenet D, D'Ari R, Bouloc P (1996) The SIGNAL experiment in BIORACK: Escherichia coli in microgravity. J Biotechnol 47:89–97
Tixador R, Richoilley G, Gasset G, Templier J, Bes JC, Moatti N, Lapchine I (1985) Study of minimal inhibitory concentration of antibiotics on bacteria cultivated in vitro in space (Cytos-2 experiment). Aviat Space Environ Med 56:748–751
Tixador R, Gasset G, Eche B, Moatti N, Lapchine L, Woldringh C, Toorop P, Moatti JP, Delmotte F, Tap G (1994) Behavior of bacteria and antibiotics under space conditions. Aviat Space Environ Med 65:551–556
Untrau-Taghian S, Lebrihi A, Germain P, Lefebvre G (1995) Influence of growth-rate and precursor availability on spiramycin production in Streptomyces ambofaciens. Can J Microbiol 41:157–162
Wilson GC, Bushell ME (1995) The induction of antibiotic-synthesis in Saccharopolyspora erythraea and Streptomyces hygroscopicus by growth-rate decrease is accompanied by a down-regulation of protein-synthesis rate. FEMS Microbiol Lett 129:89–96
Acknowledgements
This work was jointly supported by BioServe Space Technologies at the University of Colorado, Boulder, under NASA Cooperative Agreement NCC8-242, and Bristol-Myers Squibb Pharmaceutical Research Institute. Additional support for postflight analyses was provided by the Center for Faculty Development, University of Colorado, Denver. The authors would also like to thank Dr. Michael A. Poss for his support of this study and Brian Peters for his assistance with medium preparation.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Benoit, M.R., Li, W., Stodieck, L.S. et al. Microbial antibiotic production aboard the International Space Station. Appl Microbiol Biotechnol 70, 403–411 (2006). https://doi.org/10.1007/s00253-005-0098-3
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00253-005-0098-3