SeQuential: Sustainability and Growth in the Biofuels Business

SeQuential, a vertically-integrated biodiesel company based in Portland, Oregon, pursued a more sustainable supply and production strategy than many competitors by securing inputs from used cooking oil (UCO) rather than new crops. A fragmented U.S. biodiesel industry produced more than 1.25 billion gallons of the fuel in 2016 from a mix of virgin materials and UCO, but the environmental impact of crop-based biodiesel was increasingly controversial. Meanwhile, UCO collection had grown rapidly in recent years, and with strong forecasted growth, offered a potential additional revenue stream for vertically-integrated biodiesel firms. The price of the UCO used to produce SeQuential’s biodiesel and the fuel itself were driven by commodity indices, creating a highly volatile market. In addition, industry profitability was heavily reliant on government support. This support was manifested through funding for Renewable Identification Numbers (RINs) and tax credits. The recent election of a U.S. President publicly opposed to climate change mitigation, and the re-election of a sympathetic U.S. Congress, worsened perennial uncertainty around the renewal of these policies. Tyson Keever, President and CEO of SeQuential, had guided the company through a period of major growth and vertical integration by overseeing a series of regional mergers and acquisitions. As a result, the company now faced growing pains linked to employee turnover, operational integration and efficiency, and instilling a culture of sustainability in all SeQuential employees. At the same time, SeQuential was developing a new strategy for future growth, while attempting to mitigate increased regulatory and market uncertainty. In this case, students are tasked with developing a series of strategic, mission-aligned growth proposals that address these challenges

EWS-FLI1 confers exquisite sensitivity to NAMPT inhibition in Ewing sarcoma cells

Ewing sarcoma (EwS) is the second most common bone cancer in children and adolescents with a high metastatic potential. EwS development is driven by a specific chromosomal translocation resulting in the generation of a chimeric EWS-ETS transcription factor, most frequently EWS-FLI1.Nicotinamide adenine dinucleotide (NAD) is a key metabolite of energy metabolism involved in cellular redox reactions, DNA repair, and in the maintenance of genomic stability. This study describes targeting nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme of NAD synthesis, by FK866 in EwS cells. Here we report that blocking NAMPT leads to exhaustive NAD depletion in EwS cells, followed by a metabolic collapse and cell death. Using conditional EWS-FLI1 knockdown by doxycycline-inducible shRNA revealed that EWS-FLI1 depletion significantly reduces the sensitivity of EwS cells to NAMPT inhibition. Consistent with this finding, a comparison of 7 EwS cell lines of different genotypes with 5 Non-EwS cell lines and mesenchymal stem cells revealed significantly higher FK866 sensitivity of EWS-ETS positive EwS cells, with IC50 values mostly below 1nM.Taken together, our data reveal evidence of an important role of the NAMPT-mediated NAD salvage pathway in the energy homeostasis of EwS cells and suggest NAMPT inhibition as a potential new treatment approach for Ewing sarcoma.Austrian Science Fund (FWF), grant I1225-B19; European Union's FP7 project ASSET (grant agreement No. 259348); Research Manitoba and CancerCare Manitoba Foundation. Heart and Stroke Foundation of Canada (G-14-0005708). E.M.M. is the recipient of a Research Manitoba Graduate Studentship. G.M.H. is the Canada Research Chair in Molecular Cardiolipin Metabolism. J.A. is supported by Asociación Pablo Ugarte and Miguelañez S.A, ASION-La Hucha de Tomás, Fundación La Sonrisa de Alex and Instituto de Salud Carlos III (PI12/00816 and Spanish Cancer Network RTICC RD12/0036/0027).S