# Lignocellulosic Biomass as a Substrate for Oleaginous Microorganisms: A Review
## 2 Oleaginous microorganisms
### Sugar Conversion into SCO and Regulatory Mechanisms in Sugar Assimilation
Furthermore, some strains can consume more than two sugars simultaneously. For instance, strains of _Rhodosporidium_ and _Pseudozyme_ show a simultaneous consumption of glucose, xylose and fructose [115] and glucose, xylose and arabinose, respectively [116]. Likewise, _Rhodosporidium kratochvilovone_ and _Y. lipolytica_ showed a simultaneous consumption of different pentoses and hexoses on mixed sugar media [117; 118]. In addition, it has been recently documented that strains of _Meyerozyma guilliermondii_, _Scheffersomyces cojopensis_ and _Sugiyamaella paludigena_ isolated from decaying wood can simultaneously consume glucose, mannose and xylose, the most important sugars in lignocellulosic biomass [119]. In this research, significant simultaneous expression of several key enzymes, such as phosphoglucose isomerase, phosphomannose isomeraseand xylulokinase, involved in glucose, mannose, and xylose metabolism, respectively, has been reported proving simultaneous sugar consumption, although a preference for glucose was always observed [119]. A simplified scheme presenting the conversion of the most important lignocellulosic sugars into storage lipids is shown in Figure 2. Simultaneous sugar consumption can be attributed to the low carrier specialization in yeast [67]. Lipid accumulation is induced by nutrient (usually nitrogen) deficiency, which causes a reduction of adenosine monophosphate (AMP) concentration. This reduction inhibits NAD+-dependent mitochondrial isocitrate dehydrogenase (NAD+-ICDH), which is allosterically activated by AMP [1]. The inhibition of NAD+-ICDH causes a deregulation of the Krebs cycle resulting in citric acid accumulation in the mitochondria that is secreted then in the cytosol in exchange for malate. Subsequently, citric acid is converted to oxaloacetate and acetyl-CoA (the precursor of FA biosynthesis), through the action of ATP-dependent citrate lyase (ACL). It has been reported that a low or null activity of ICDH and a high activity of ACL in the cytoplasm are key factors for the accumulation of lipids [2; 5; 6; 44; 119; 120; 121; 122; 123]. The process of FA synthesis is carried through the FA synthase complex. First enzyme involved is acetyl-CoA carboxylase (ACC) that converts acetyl-CoA to malonyl-CoA, reaction that frequently takes place in the cytosol of heterotrophic organisms and in the plastid of autotrophic microorganisms, and in some cases in both [3]. Then malonyl elongation is catalyzed by adding 2 carbons to the carbon chain, consuming 2 NADPH molecules per elongation unit in eukaryotes, while in autotrophic bacteria and algae the FAS type II enzyme complex catalytically elongates the lipid chains by two carbon units in an iterative pathway [4; 124; 125]. FA synthesis requires high reducing power in the form of NADPH. In oleaginous bacteria NADPH is provided by PPP [126], while in oleaginous eukaryotes NADPH is provided by both, the malic enzyme (ME) reaction that converts malate to pyruvate and the PPP [5; 6; 127; 128; 129]. In oleaginous microalgae the main donor of reducing power seems to be the ferredoxin NADP reductase of the photosystem I [6]. Following long chain acyl-CoA synthesis in the cytoplasm, acyl-CoA is transported to the endoplasmic reticulum (ER) and esterified with glycerol-3-phosphate (G3P), generating structural (phospholipids, glycolipids) and storage (TAG) lipids through the Kennedy pathway [5; 72; 130; 131; 132]. Figure 2: Simplified scheme of glucose, mannose, and xylose catabolism and principal enzymes involved in lipid biosynthesis. The key-enzymes considered in this study are highlighted in green. ICDH, NAD+-dependent isocitrate dehydrogenase; PGI, phosphoglucose isomerase; PMI, phosphomannose isomerase; XK, xylulokinase; ATP:CL, ATP citrate lyase (from [PERSON] et al. [119], Reproduced with permission from Applied Biochemistry and Biotechnology, Springer Nature, 2020). G3P is the second precursor molecule of TAG and therefore its availability is believed to affect TAG biosynthesis [133].