{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T01:54:22Z","timestamp":1774922062813,"version":"3.50.1"},"reference-count":69,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2001,7,25]],"date-time":"2001-07-25T00:00:00Z","timestamp":996019200000},"content-version":"vor","delay-in-days":205,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Chemical Record"],"published-print":{"date-parts":[[2001,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We have studied microbial secondary metabolism in a simulated microgravity (SMG) environment provided by NASA rotating\u2010wall bioreactors (RWBs). These reactors were designed to simulate some aspects of actual microgravity that occur in space. Growth and product formation were observed in SMG in all cases studied, i.e., <jats:italic>Bacillus brevis<\/jats:italic> produced gramicidin S (GS), <jats:italic>Streptomyces clavuligerus<\/jats:italic> made \u03b2\u2010lactam antibiotics, <jats:italic>Streptomyces hygroscopicus<\/jats:italic> produced rapamycin, and <jats:italic>Escherichia coli<\/jats:italic> produced microcin B17 (MccB17). Of these processes, only GS production was unaffected by SMG; production of the other three products was inhibited. This was determined by comparison with performance in an RWB positioned in a different mode to provide a normal gravity (NG) environment. Carbon source repression by glycerol of the GS process, as observed in shaken flasks, was not observed in the RWBs, whether operated in the SMG or NG mode. The same phenomenon occurred in the case of MccB17 production, with respect to glucose repression. Thus, the negative effects of carbon source on GS and \u03b2\u2010lactam formation are presumably dependent on shear, turbulence, and\/or vessel geometry, but not on gravity. Stimulatory effects of phosphate and the precursor <jats:sc>l<\/jats:sc>\u2010lysine on \u03b2\u2010lactam antibiotic production, as observed in flasks, also occurred in SMG. An almost complete shift in the localization of produced MccB17 from cells to extracellular medium was observed when <jats:italic>E. coli<\/jats:italic> was grown in the RWB under SMG or NG. If a plastic bead was placed in the RWB, accumulation became cellular, as it is in shaken flasks, indicating that sheer stress favors a cellular location. In the case of rapamycin, the same type of shift was observed, but it was less dramatic, i.e., growth in the RWB under SMG shifted the distribution of produced rapamycin from 2\/3 cellular:1\/3 extracellular to 1\/3 cellular:2\/3 extracellular. Stress has been shown to induce or promote secondary metabolism in a number of other microbial systems. RWBs provide a low stress SMG environment, which, however, supports only poor production of MccB17, as compared to production in shaken flasks. We wondered whether the poor production in RWBs under SMG is due to the low level of stress, and whether increasing stress in the RWBs would raise the amount of MccB17 formed. We found that increasing shear stress by adding a single Teflon\u2122 bead to the RWB improved MccB17 production. Although shear stress seems to have a marked positive effect on MccB17 production in SMG, addition of various concentrations of ethanol to RWBs (or to shaken flasks) failed to increase MccB17 production. Ethanol stress merely decreased production and, at higher concentrations, inhibited growth. Interestingly, cells growing in the RWB were much more resistant to the growth\u2010 and production\u2010inhibitory effects of ethanol than cells growing in shaken flasks. With respect to <jats:italic>S. hygroscopicus<\/jats:italic>, addition of Teflon\u2122 beads to the RWB reversed the inhibition of growth, but rapamycin production was still markedly inhibited, and the distribution did not revert back to a preferential cellular site. \u00a9 2001 John Wiley &amp; Sons, Inc. and The Japan Chemical Journal Forum Chem Rec 1:333\u2013346, 2001<\/jats:p>","DOI":"10.1002\/tcr.1018","type":"journal-article","created":{"date-parts":[[2002,9,10]],"date-time":"2002-09-10T23:33:12Z","timestamp":1031700792000},"page":"333-346","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["Secondary metabolism in simulated microgravity"],"prefix":"10.1002","volume":"1","author":[{"given":"Arnold 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