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  • br DGAT proteins lipid droplets and cancer cells

    2019-10-29


    DGAT proteins, lipid droplets and cancer cells
    Conclusions and future directions
    Conflicts of interest
    Acknowledgements This work was supported by NIH grants GM062887, P01CA097132, and Veterans Affairs Merit Award to LMO.
    Introduction Bioethanol and biodiesel are regarded as the two major liquid biofuels that are feasible for large-scale production to replace petroleum-based compounds in internal combustion engines. Of the two, biodiesel requires fewer modifications to current diesel engines, which means that switching to biodiesel will lead to minimal disruptions to current transportation networks. In fact, biodiesel has several advantages over petroleum-based diesel including reduced carbon monoxide emissions and higher combustion efficiency (Demirbas, 2007). In addition, the infrastructure to handle the mass-production of biodiesel is already in place, due to the fact that biodiesel can be stored and transported via current petroleum infrastructure, unlike bioethanol or hydrogen (Demirbas, 2008). While biodiesel derived from storage lipids, such as triacylglyercols (TAGs) from major crop plants oilseed rape, soy and oil palm, is theoretically capable of providing a large proportion of our current energy needs, there have been several studies that have highlighted major problems that could arise due to land/resource use competition, net carbon emissions, and the trade-off between producing food versus fuel. Algal-based biofuels have thus been suggested as a partial solution to this problem (Chisti, 2008). Microalgae have much higher nitric oxide inhibitor productivity compared to most higher plants, and some algal species have been known to accumulate up to 75% of their dry mass in lipids (Banerjee et al., 2002, Scott et al., 2010, Sivakumar et al., 2010). Algal growth facilities do not need to be built on arable land, and could potentially be located in aquatic environments. Coupling this with the use of marine algal species for biodiesel production would also sidestep the issue of increasing competition for farmland and fresh water. At the moment mass-production of microalgae is hampered by problems that stem from trying to scale up microalgal growth experiments in the lab to outdoor ponds or large bioreactors. In addition to problems dealing with agronomy, finding algal strains that can be selectively optimised for both high biomass productivity and high TAG content has proven to be difficult (Sheehan, 1998). The fatty acid composition of TAGs produced by microalgae is also of great interest, as different fatty acids vary significantly in their characteristics (Klopfenstein and Walker, 1983). While bio-prospecting and strain selection under positive pressure could be used to find the optimum algal strain for mass-production of biofuels, it is likely that genetic engineering of nearly optimal strains will prove to be faster and more efficient in terms of optimisation of TAG composition. However, we need to have a better understanding of how TAG biosynthesis is controlled in algae if we are to begin rational and targeted genetic modifications to increase and improve TAG productivity (Radakovits et al., 2010). In this paper, we will outline TAG biosynthesis in higher plants, with particular emphasis on the standard Kennedy pathway (Kresge et al., 2005), as the basis for consideration of TAG biosynthesis in algae. Then we will focus on the enzyme diacylglycerol acyltransferase (DGAT), which catalyses the last step in TAG biosynthesis in the Kennedy pathway. We have searched several sequenced algal genomes for DGAT homologues and we find that most algal genomes seem to have multiple DGAT isoforms, which is rare in other eukaryotes.
    Enzymology of TAG biosynthesis
    In search of algal DGATs
    Discussion It has been assumed that algal fatty acid and TAG biosynthesis would be similar to that of higher plants, and indeed in silico analysis reveals many sequences in algal genomes that are likely to encode the relevant enzymes for fatty acid biosynthesis and TAG biosynthesis (Hu et al., 2008, Miller et al., 2010). However, it is becoming clear that for most algal species, even for those that fall into the green algal lineage, there are some notable differences.