Please use this identifier to cite or link to this item: https://doi.org/10.1021/acsomega.8b01620
Title: Synthetic Enzymology and the Fountain of Youth: Repurposing Biology for Longevity
Authors: Lim, Yan Ping 
Go, Maybelle K 
Raida, Manfred 
Inoue, Takao 
Wenk, Markus R 
Keasling, Jay D
Chang, Matthew W 
Yew, Wen Shan 
Keywords: Science & Technology
Physical Sciences
Chemistry, Multidisciplinary
Chemistry
III POLYKETIDE SYNTHASES
CAENORHABDITIS-ELEGANS
CALORIC RESTRICTION
DIETARY RESTRICTION
LIFE-SPAN
CHALCONE SYNTHASE
OXIDATIVE STRESS
RESVERATROL
RESPIRATION
BIOSYNTHESIS
Issue Date: 2018
Publisher: AMER CHEMICAL SOC
Citation: Lim, 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
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.
Source Title: ACS OMEGA
URI: https://scholarbank.nus.edu.sg/handle/10635/170654
ISSN: 24701343
24701343
DOI: 10.1021/acsomega.8b01620
Appears in Collections:Staff Publications
Elements

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
61. Synthetic Enzymology and the Fountain of Youth.pdfPublished version2.58 MBAdobe PDF

OPEN

PublishedView/Download

SCOPUSTM   
Citations

1
checked on May 21, 2022

Page view(s)

156
checked on May 12, 2022

Download(s)

2
checked on May 12, 2022

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.