Please use this identifier to cite or link to this item: https://doi.org/10.1021/acsomega.8b01620
DC FieldValue
dc.titleSynthetic Enzymology and the Fountain of Youth: Repurposing Biology for Longevity
dc.contributor.authorLim, Yan Ping
dc.contributor.authorGo, Maybelle K
dc.contributor.authorRaida, Manfred
dc.contributor.authorInoue, Takao
dc.contributor.authorWenk, Markus R
dc.contributor.authorKeasling, Jay D
dc.contributor.authorChang, Matthew W
dc.contributor.authorYew, Wen Shan
dc.date.accessioned2020-06-22T08:23:12Z
dc.date.available2020-06-22T08:23:12Z
dc.date.issued2018
dc.identifier.citationLim, Yan Ping, Go, Maybelle K, Raida, Manfred, Inoue, Takao, Wenk, Markus R, Keasling, Jay D, Chang, Matthew W, Yew, Wen Shan (2018). Synthetic Enzymology and the Fountain of Youth: Repurposing Biology for Longevity. ACS OMEGA 3 (9) : 11050-11061. ScholarBank@NUS Repository. https://doi.org/10.1021/acsomega.8b01620
dc.identifier.issn24701343
dc.identifier.issn24701343
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/170654
dc.description.abstract© 2018 American Chemical Society. Caloric restriction (CR) is an intervention that can increase maximal lifespan in organisms, but its application to humans remains challenging. A more feasible approach to achieve lifespan extension is to develop CR mimetics that target biochemical pathways affected by CR. Recent studies in the engineering and structural characterization of polyketide synthases (PKSs) have facilitated their use as biocatalysts to produce novel polyketides. Here, we show that by establishing a combinatorial biosynthetic route in Escherichia coli and exploring the substrate promiscuity of a mutant PKS from alfalfa, 413 potential anti-ageing polyketides were biosynthesized. In this approach, novel acyl-coenzyme A (CoA) precursors generated by promiscuous acid-CoA ligases were utilized by PKS to generate polyketides which were then fed to Caenorhabditis elegans to study their potential efficacy in lifespan extension. It was found that CR mimetics like resveratrol can counter the age-associated decline in mitochondrial function and increase the lifespan of C. elegans. Using the mitochondrial respiration profile of C. elegans supplemented for 8 days with 50 μM resveratrol as a blueprint, we can screen our novel polyketides for potential CR mimetics with improved potency. This study highlights the utility of synthetic enzymology in the development of novel anti-ageing therapeutics.
dc.language.isoen
dc.publisherAMER CHEMICAL SOC
dc.sourceElements
dc.subjectScience & Technology
dc.subjectPhysical Sciences
dc.subjectChemistry, Multidisciplinary
dc.subjectChemistry
dc.subjectIII POLYKETIDE SYNTHASES
dc.subjectCAENORHABDITIS-ELEGANS
dc.subjectCALORIC RESTRICTION
dc.subjectDIETARY RESTRICTION
dc.subjectLIFE-SPAN
dc.subjectCHALCONE SYNTHASE
dc.subjectOXIDATIVE STRESS
dc.subjectRESVERATROL
dc.subjectRESPIRATION
dc.subjectBIOSYNTHESIS
dc.typeArticle
dc.date.updated2020-06-17T04:56:24Z
dc.contributor.departmentDEPT OF BIOCHEMISTRY
dc.contributor.departmentLIFE SCIENCES INSTITUTE
dc.description.doi10.1021/acsomega.8b01620
dc.description.sourcetitleACS OMEGA
dc.description.volume3
dc.description.issue9
dc.description.page11050-11061
dc.published.statePublished
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