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Fig. 3 | Microbial Cell Factories

Fig. 3

From: “Metabolic burden” explained: stress symptoms and its related responses induced by (over)expression of (heterologous) proteins in Escherichia coli

Fig. 3

Overview of the stress responses induced by the expression of membrane proteins. The top figure shows the situation in unstressed cells: (i) Co-translational insertion of proteins into the membrane; (ii) Post-translational translocation of proteins across the IM; (iii) Degradation of \(\sigma ^{\textrm{S}}\) and \(\sigma ^{\textrm{H}}\) by ClpXP and FtsH respectively; (iv) Translational inhibition of ibpAB and rpoH by IbpA; (v) \(\sigma ^{\textrm{E}}\) is kept inactive by RseA; (vi) CpxP prevents the activity of CpxA; (vii) PspA binds PspF to inhibit transcriptional activation. The bottom figure gives an overview of how expression of MP induces stress and how different stress mechanisms are connected. Effect on the cell: (1) Stalling of proteins that need to be inserted in or translocated across the IM; (2) Aggregation of secretory proteins and formation of IB; (3) Misfolding of IM proteins; (4) Stress at the OM due to changed composition; (5) Stress at the IM due to changed composition. Stress mechanisms: (a) Chaperones and sHSP co-aggregate with the IB for refolding and degradation; (b) Translational inhibition of ibpAB and rpoH by IbpA is lifted; (c) Transcriptional acitivation of ibpAB by \(\sigma ^{\textrm{H}}\); (d) Sequestration of chaperones by IB induces misfolding of cytoplasmic proteins; (e) Release of \(\sigma ^{\textrm{E}}\) by proteolysis of RseA; (f) Transcriptional activation of rpoH by \(\sigma ^{\textrm{E}}\) and CpxR; (g) Activation of sRNAs micA and rybB; (h) Induction of DSB by \(\sigma ^{\textrm{E}}\); (i) Activation of sensor kinase CpxA, activating the transcriptional regulator CpxR; (j) Activation of transcription of cpxP; (k) Sequestration of CpxP by misfolded proteins and degradation by DegP; (l) Transcription of the sRNA cpxQ; (m) Translational activation of rpoS by the sRNA rprA; (n) Release of PspF and transcriptional activation of psp operon; (o) Positioning of PspA at the membrane and interaction with PspB an PspC; (p) Increased production of acetate via activation of different pathways. ppGpp guanosine tetra- and pentaphosphate, IM inner membrane, IB Inclusion bodies, OM outer membrane, DSB double stranded DNA break, sRNA small RNA, sHSP small heat shock protein. Gene structures are displayed according to the SBOL guidelines [6]

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