Genome-modified bacterial strains for large scale bioprocesses
AssigneesUniversity of Stuttgart, Manus Bio Inc.
InventorsMartin ZIEGLER, Ralf TAKORS, Joana SIEMEN, Michael LÖFFLER, Christine Nicole S. SANTOS, Ajikumar Parayil KUMARAN
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Abstract
The present invention in various aspects and embodiments provides engineered bacterial strains having a modified genome that provides advantages in maintenance and biosynthetic processes when cultured at large scale. The present invention further provides methods for large-scale fermentation using the bacterial strains. In various embodiments, the strain engineering yields a reduction in cellular responses to micro-environmental stimuli imposed in large scale bioreactors.
Claims106
A genome-modified bacterial strain comprising deletions or inactivations of at least ten non-essential genes coding for two or more of:
- flagella components or transcriptional regulators thereof, chemotaxis proteins and regulators thereof, inhibitors of DNA replication, and proteins involved in active transport of sugars other than glucose;
- the strain exhibiting advantages in maintenance and biosynthesis performance under large-scale conditions as compared to a parent strain that does not contain said deletions.
A genome-modified E. coli strain comprising at least 10 gene deletions or inactivations, including a plurality of deletions or inactivations selected from, rpoS, hupB, clpB, uhpT, clpA, yeeI, htpG, motA, argT, rplP, flxA, fadD, pheT, flgM, arcA, modA, leuD, fumA, yjcZ, gpmA, rpoE, rseA, maeB, katG, ychH, hns, ygaT, cheW, ybhQ, atpC, glyS, fadB, osmE, hcaR, uspE, uspA, dps, ygeV, pheA, yfiQ, ibpA, ihfB, livK, miaA, ihfA, cysA, bolA, ydcS, ucpA, uspF, nuoH, yeaA, yjjY, aldB, yeaG, araC, yqfA, grpE, aroP, sra, ygjG, cheY, acrB, tpx, cysN, yaeH, osmC, ugpB, ykfB, Smg, yfcY, hypD, elaB, rsd, ybaL, fadH, ubiA, ygaU, sseA, yccV, bfr, pheS, yihX, ytfQ, putP, cycA, yeaT, yiiU, ycgB, rrmJ, rob, agp, ybeL, lrp, ydhR, malP, fbaB, msyB, glcC, ydcJ, ubiC, lon, glpK, dacC, yqjC, glmM, ompR, selD, ygdH, trpA, mukB, nupG, gltD, uspG, yggG, yrbL, glcD, cfa, phoH, yniA, gst, mscL, yhiO, ybhL, yahO, yjgD, glpF, wbbK, yfcX, yqjD, paaJ, yqjE, ynjH, aroL, galS, fruA, mhpR, rnr, prlC, smf, ygaM, ynhG, glgC, csiE, yaiZ, ygiN, aphA, ivy, glgS, ybjP, puuD, udp, yceP, fxsA, ybbN, yhbT, yeaY, ybeZ, ycjG, erfK, yhaO, yjdC, astC, sbmC, yghZ, ydbJ, uxuA, yhaL, fucO, ygdR, yajO, elbB, yhdW, ytfJ, ygg, ycfP, yfbT, phoU, blc, pepT, yqcA, yegP, yghU, sfsA, ysgA, yohC, mgtA, ybbK, nhaA, adhP, yehZ, rmuC, ydeW, yqeC, yecA, mppA, treA, dkgA, malS, ddlB, yafY, exuR, yhjY, yfbU, nadR, ydgD, qor, slt, yjgB, yaiE, soxS, prpR, yeiE, yahK, ydjF, yjfO, talA, yodD, pmrD, yhdH, yliB, yliJ, yeeZ, yaeP, ybdK, msrA, ydhQ, rfaB, ybjQ, ygiE, grxB, yjjM, ydhF, ycbB, araF, ygjR, yqjG, cdaR, ymgE, glnG, deoC, ddpX, otsB, yhfZ, pheL, gmr, yibF, hdhA, ygdI, cysQ, yfdY, yceK, ydhC, yqjI, glpD, ydiZ, yhhA, yibT, ygjF, tam, yjfN, yacL, melR, yiaG, yjeF, ycfX, yiiT, kbl, dhaH, yafV, ycjX, ego, ytfR, sodC, ybaE, tdh, yhjD, fic, rpiB, ibpB, ytfN, yfiL, araB, relB, yadH, mrdB, ybiH, frwC, yjbR, psiF, basR, xylA, melA, ybhG, yhcO, garP, nlpE, ampE, ydaN, ydbC, pdxJ, glpT, fucA, yjbB, srlA, yddH, ybjK, yjgK, yadI, yncB, idi, sufA, zntR, ade, ynfD, yncG, yhcH, yhfY, yafM, yhhW, ybiI, yibI, ybeH, and ysaB.
Dependencies are inferred from the claim text.