Sze, Y. | bioRxiv Science

bioRxiv2020

Enhanced inhibitor tolerance and increased lipid productivity through adaptive laboratory evolution in the oleaginous yeast Metshnikowia pulcherrima

Microbial lipid production from second generation feedstocks presents a sustainable route to future fuels, foods and bulk chemicals. The oleaginous yeast Metshnikowia pulcherrima has previously been investigated as a potential platform organism for lipid production due to its ability to be grown in non-sterile conditions and metabolising a wide range of oligo- and monosaccharide carbon sources within lignocellulosic hydrolysates. However, the generation of inhibitors from depolymerisation causes downstream bioprocessing complications, and despite M. pulcherrimas comparative tolerance, their presence is deleterious to both biomass and lipid formation. Using either a single inhibitor (formic acid) or an inhibitor cocktail (formic acid, acetic acid, fufural and HMF), two strategies of adaptive laboratory evolution were performed to improve M. pulcherrimas fermentation inhibitor tolerance. Using a sequential batch culturing approach, the resulting strains from both strategies had increased growth rates and reduced lag times under inhibiting conditions versus the progenitor. Interestingly, the lipid production of the inhibitor cocktail evolved strains markedly increased, with one strain producing 41% lipid by dry weight compared to 22% of the progenitor. The evolved species was cultured in a non-sterile 2L stirred tank bioreactor and accumulated lipid rapidly, yielding 6.1 g/L of lipid (35% cell dry weight) within 48 hours; a lipid productivity of 0.128 g L-1 h-1. Furthermore, the lipid profile was analogous to palm oil, consisting of 39% C16:0 and 56% C18:1 after 48 hours.

bioengineering↗

bioRxiv2019

Maternal antioxidant treatment prevents behavioural and neural changes in offspring exposed to prenatal social stress

Maternal exposure to social stress during pregnancy is associated with an increased risk of psychiatric disorders in the offspring in later life. However, the mechanism through which the effects of maternal stress are transmitted to the foetus is unclear. Using a rat model, we explored the mechanisms by which maternal social stress is conveyed to the foetus and the potential for targeted treatment to prevent disease in the offspring. Maternal stress increased circulating corticosterone in the mother, but not the foetuses. Maternal stress also induced oxidative stress in the placenta, but not in the foetal brain, and this was prevented by administration of a nanoparticle-bound antioxidant. Moreover, antioxidant treatment prevented prenatal stress-induced anxiety-like behaviour in the adult male offspring, along with several stress-induced neuroanatomical, neurochemical and gene expression changes in the offspring brain. Importantly, many of these neural effects were mimicked in neuronal cultures by application of placental-conditioned medium or foetal plasma from stressed pregnancies. Both placental-conditioned medium and foetal plasma contained differentially abundant extracellular microRNAs following prenatal stress. The present study highlights the crucial role of the placenta, and the molecules it secretes, in foetal brain development and provides evidence of the potential for treatment that can prevent maternal stress-induced foetal programming of neurological disease.

neuroscience↗