TY - JOUR
T1 - Synthetic tolerance
T2 - Three noncoding small RNAs, DsrA, ArcZ and RprA, acting supra-additively against acid stress
AU - Gaida, Stefan M.
AU - Al-Hinai, Mohab A.
AU - Indurthi, Dinesh C.
AU - Nicolaou, Sergios A.
AU - Papoutsakis, Eleftherios T.
N1 - Funding Information:
National Science Foundation (NSF) (USA) [CBET-1033926]. Funding for open access charge: NSF [CBET-1033926].
PY - 2013/10
Y1 - 2013/10
N2 - Synthetic acid tolerance, especially during active cell growth, is a desirable phenotype for many biotechnological applications. Natively, acid resistance in Escherichia coli is largely a stationary-phase phenotype attributable to mechanisms mostly under the control of the stationary-phase sigma factor RpoS. We show that simultaneous overexpression of noncoding small RNAs (sRNAs), DsrA, RprA and ArcZ, which are translational RpoS activators, increased acid tolerance (based on a low-pH survival assay) supra-additively up to 8500-fold during active cell growth, and provided protection against carboxylic acid and oxidative stress. Overexpression of rpoS without its regulatory 5′-UTR resulted in inferior acid tolerance. The supra-additive effect of overexpressing the three sRNAs results from the impact their expression has on RpoS-protein levels, and the beneficial perturbation of the interconnected RpoS and H-NS networks, thus leading to superior tolerance during active growth. Unlike the overexpression of proteins, overexpression of sRNAs imposes hardly any metabolic burden on cells, and constitutes a more effective strain engineering strategy.
AB - Synthetic acid tolerance, especially during active cell growth, is a desirable phenotype for many biotechnological applications. Natively, acid resistance in Escherichia coli is largely a stationary-phase phenotype attributable to mechanisms mostly under the control of the stationary-phase sigma factor RpoS. We show that simultaneous overexpression of noncoding small RNAs (sRNAs), DsrA, RprA and ArcZ, which are translational RpoS activators, increased acid tolerance (based on a low-pH survival assay) supra-additively up to 8500-fold during active cell growth, and provided protection against carboxylic acid and oxidative stress. Overexpression of rpoS without its regulatory 5′-UTR resulted in inferior acid tolerance. The supra-additive effect of overexpressing the three sRNAs results from the impact their expression has on RpoS-protein levels, and the beneficial perturbation of the interconnected RpoS and H-NS networks, thus leading to superior tolerance during active growth. Unlike the overexpression of proteins, overexpression of sRNAs imposes hardly any metabolic burden on cells, and constitutes a more effective strain engineering strategy.
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U2 - 10.1093/nar/gkt651
DO - 10.1093/nar/gkt651
M3 - Article
C2 - 23892399
AN - SCOPUS:84885943611
SN - 0305-1048
VL - 41
SP - 8726
EP - 8737
JO - Nucleic Acids Research
JF - Nucleic Acids Research
IS - 18
ER -