Biology subjects

Chow, J. Y.

Publications and source records attributed to Chow, J. Y..

3 recordsLinked to original sources

bioRxiv2025

Metabolic engineering approach to boost γ-decalactone production in S. cerevisiae identifies a critical role for the peroxisomal Fatty Acyl-CoA Synthetase Faa2

Lactones constitute a family of aroma compounds found in fruits, flowers and vegetables and are in high demand in the food industry. Previous studies have reported biotransformation of castor beans-extracted ricinoleic acid to {gamma}-decalactone using oleaginous yeast Yarrowia lipolytica. Given the potential toxicities associated with castor beans, we have used a metabolic flux-engineering approach to produce {gamma}-decalactone from oleic acid in Saccharomyces cerevisiae. Intracellular conversion of oleic acid to ricinoleic acid was achieved by the expression of oleate hydroxylase Fah12 from ergot fungus Claviceps purpurea. Glycerol-3-phosphate dehydrogenase-mediated glycerol synthesis was identified as the major metabolic diversion of oleic acid that negatively impacts {gamma}-decalactone yields. Chemogenomic profiling analysis revealed that the tryptophan biosynthetic pathway provides resistance to {gamma}-decalactone-mediated toxicity in yeast. Overexpression of tryptophan transporter Tat1 enhanced {gamma}-decalactone production by about 3- fold. Deficiency of genes encoding the cytoplasmic fatty acyl CoA synthetases FAA1 or FAA4 alone did not significantly influence {gamma}-decalactone production. However, deficiency of peroxisomal FAA2 drastically diminished the yield of {gamma}-decalactone. Thus, this study uncovers the metabolic barriers to oleic acid-to-{gamma}-decalactone conversion and identifies Faa2 as an essential element in this biotransformation.

synthetic biology↗

bioRxiv2024

Wolbachia incompatible insect technique program optimization over large spatial scales using a process-based model of mosquito metapopulation dynamics

BackgroundWolbachia incompatible insect technique (IIT) programs have been shown in field trials to be highly effective in suppressing populations of mosquitoes that carry diseases such as dengue, chikungunya and Zika. However, the frequent and repeated release of Wolbachia-infected male mosquitoes makes such programs resource-intensive. While the need for optimization is recognized, potential strategies to optimize releases and reduce resource utilization have not been fully explored. MethodsWe developed a process-based model to study the spatial-temporal metapopulation dynamics of mosquitoes in a Wolbachia IIT program, which explicitly incorporates climatic influence in mosquito life-history traits. We then used the model to simulate various scale-down and redistribution strategies to optimize the existing program in Singapore. Specifically, the model was used to study the trade-offs between the intervention efficacy outcomes and resource requirements of various release program strategies, such as the total number of release events and the number of mosquitoes released. ResultsWe found that scaling down releases in existing sites from twice a week to only once a week yielded minimal changes in suppression efficacy (from 91% to 85%), while requiring 45% fewer mosquitoes and release events. Additionally, redistributing mosquitoes from already suppressed areas and releasing them in new areas once a week led to a greater total suppressive efficacy (88% compared to 65%) while also yielding a 16% and 14% reduction in the number of mosquitoes and release events required respectively. ConclusionsBoth scale-down and redistribution strategies can be implemented to significantly reduce program resource requirements without compromising the suppressive efficacy of IIT. These findings will inform planners on ways to optimize existing and future IIT programs, potentially allowing for the wider adoption of this method for mosquito-borne disease control.

ecology↗

bioRxiv2021

SARS-CoV-2-specific memory B cells can persist in the elderly despite loss of neutralising antibodies

Memory B cells (MBC) can provide a recall response able to supplement waning antibodies with an affinity-matured response better able to neutralise variant viruses. We studied a cohort of vulnerable elderly care home residents and younger staff, a high proportion of whom had lost neutralising antibodies (nAb), to investigate their reserve immunity from SARS-CoV-2-specific MBC. Class-switched spike and RBD-tetramer-binding MBC with a classical phenotype persisted five months post-mild/asymptomatic SARS-CoV-2 infection, irrespective of age. Spike/RBD-specific MBC remained detectable in the majority who had lost nAb, although at lower frequencies and with a reduced IgG/IgA isotype ratio. Functional spike/S1/RBD-specific recall was also detectable by ELISpot in some who had lost nAb, but was significantly impaired in the elderly, particularly to RBD. Our findings demonstrate persistence of SARS-CoV-2-specific MBC beyond loss of nAb, but highlight the need for careful monitoring of functional defects in RBD-specific B cell immunity in the elderly. One sentence summaryCirculating class-switched spike and RBD-specific memory B cells can outlast detectable neutralising antibodies but are functionally constrained in the elderly.

immunology↗