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• W4281729586 startingPage "18331" @default.
• W4281729586 abstract "Heterologous production of limonene in microorganisms through the mevalonate (MVA) pathway has traditionally imposed metabolic burden and reduced cell fitness, where imbalanced stoichiometries among sequential enzymes result in the accumulation of toxic intermediates. Although prior studies have shown that changes to mRNA stability, RBS strength, and protein homology can be effective strategies for balancing enzyme levels in the MVA pathway, testing different variations of these parameters often requires distinct genetic constructs, which can exponentially increase assembly costs as pathways increase in size. Here, we developed a multi-input transcriptional circuit to regulate the MVA pathway, where four chemical inducers, l-arabinose (Ara), choline chloride (Cho), cuminic acid (Cuma), and isopropyl β-d-1-thiogalactopyranoside (IPTG), each regulate one of four orthogonal promoters. We tested modular transcriptional regulation of the MVA pathway by placing this circuit in an engineered Escherichia coli marionette strain, which enabled systematic and independent tuning of the first three enzymes (AtoB, HMGS, and HMGR) in the MVA pathway. By systematically testing combinations of chemical inducers as inputs, we investigated relationships between the expressions of different MVA pathway submodules, finding that limonene yields are sensitive to the coordinated transcriptional regulation of HMGS and HMGR." @default.
• W4281729586 created "2022-06-13" @default.
• W4281729586 creator A5035397475 @default.
• W4281729586 creator A5054515660 @default.
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• W4281729586 date "2022-05-26" @default.
• W4281729586 modified "2023-09-30" @default.
• W4281729586 title "Transcriptional Tuning of Mevalonate Pathway Enzymes to Identify the Impact on Limonene Production in <i>Escherichia coli</i>" @default.
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• W4281729586 doi "https://doi.org/10.1021/acsomega.2c00483" @default.
• W4281729586 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/35694509" @default.
• W4281729586 hasPublicationYear "2022" @default.
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