There is a second copy of spo0A in C. thermocellum, Cthe_0812 which is significantly downregulated by an unknown mechanism in standard conditions compared to the WT. The spo0A protein is activated when phosphorylated and has been shown to regulate sporulation in a number of clostridia [34]. Although, it is rare for C. thermocellum to go into sporulation, it has been shown that sporulation will occur under vitamin limitation, oxygen stress GSK690693 cell line and switching between soluble and insoluble substrates [35]. The PM growth kinetics is consistent with other

spo0A defective mutants which continue to grow under nutrient limiting conditions [36–39]. The second reason for a reduction in the expression of sporulation genes may be that the PM differentially expresses the sigma factors that control Tozasertib sporulation. The five known sporulation sigma factors

in B. Milciclib subtilis are σE, σF, σG, σH and σK [31,34]. In B. subtilis, σH is the earliest sporulation sigma factor [34]. σE is the mother cell-specific sigma factor and is also involved in the synthesis of σK, the late-acting mother cell sigma factor [31]. Furthermore, σF – dependent transcription appears to be limited to the early expression of forespore-specific genes and σG appears to encode products that are synthesized within the forespore compartment during the later stages of sporulation to enhance spore survival and facilitate germination [31]. There are six genes that encode the various sporulation sigma factors in C. thermocellum. The PM has increased expression in σE (Cthe_0447) and σF (Cthe_0120), and decreased expression in σE (Cthe_0446) for the late-log time point, and decreased expression of σK (Cthe_1012) for both time points in the standard medium comparison (Table 1). The PM has increased expression of σE (Cthe_0447) and σF (Cthe_0120) for the mid-log time point and decreased expression of σK (Cthe_1012) for both time points in the hydrolysate medium comparison (Table 1). A recent study of C.

acetobutylicum showed that σK is involved in both early and late sporulation [40]. In C. acetobutylicum sigK deletion blocks sporulation, prior to Spo0A expression and the mutant suffered from premature Farnesyltransferase cell death due to excessive medium acidification in batch cultures without pH control [40]. The sigK defective mutant did not transition into stationary phase where cells re-assimilate the acids and produce acetone, butanol, and ethanol [40]. The results suggest a positive-feedback loop between Spo0A and σK which may be the mechanism that down regulates Cthe_0812 for the PM in standard medium compared to the WT [40]. Sporulation is an energy intensive function requiring transcription of a large number of genes. By reducing the expression of certain sporulation genes, the PM may be capable of devoting more resources to growth. Furthermore, it has been shown that C.