caa a22 4500 60550413X CHVBK 20210128100614.0 cr unu---uuuuu 210128e20150401xx s 000 0 eng 10.1007/s00253-015-6450-3 doi (NATIONALLICENCE)springer-10.1007/s00253-015-6450-3 Allopurinol-mediated lignocellulose-derived microbial inhibitor tolerance by Clostridium beijerinckii during acetone-butanol-ethanol (ABE) fermentation [Elektronische Daten] [Victor Ujor, Chidozie Agu, Venkat Gopalan, Thaddeus Ezeji] In addition to glucans, xylans, and arabinans, lignocellulosic biomass hydrolysates contain significant levels of nonsugar components that are toxic to the microbes that are typically used to convert biomass to biofuels and chemicals. To enhance the tolerance of acetone-butanol-ethanol (ABE)-generating Clostridium beijerinckii NCIMB 8052 to these lignocellulose-derived microbial inhibitory compounds (LDMICs; e.g., furfural), we have been examining different metabolic perturbation strategies to increase the cellular reductant pools and thereby facilitate detoxification of LDMICs. As part of these efforts, we evaluated the effect of allopurinol, an inhibitor of NAD(P)H-generating xanthine dehydrogenase (XDH), on C. beijerinckii grown in furfural-supplemented medium and found that it unexpectedly increased the rate of detoxification of furfural by 1.4-fold and promoted growth, butanol, and ABE production by 1.2-, 2.5-, and 2-fold, respectively. Since NAD(P)H/NAD(P)+ levels in C. beijerinckii were largely unchanged upon allopurinol treatment, we postulated and validated a possible basis in DNA repair to account for the solventogenic gains with allopurinol. Following the observation that supplementation of allopurinol in the C. beijerinckii growth media mitigates the toxic effects of nalidixic acid, a DNA-damaging antibiotic, we found that allopurinol elicited 2.4- and 6.7-fold increase in the messenger RNA (mRNA) levels of xanthine and hypoxanthine phosphoribosyltransferases, key purine-salvage enzymes. Consistent with this finding, addition of inosine (a precursor of hypoxanthine) and xanthine led to 1.4- and 1.7-fold increase in butanol production in furfural-challenged cultures of C. beijerinckii. Taken together, our results provide a purine salvage-based rationale for the unanticipated effect of allopurinol in improving furfural tolerance of the ABE-fermenting C. beijerinckii. Springer-Verlag Berlin Heidelberg, 2015 Clostridium beijerinckii nationallicence Butanol nationallicence Furfural nationallicence Allopurinol nationallicence Xanthine dehydrogenase nationallicence Ujor Victor Department of Animal Sciences, The Ohio State University, and Ohio State Agricultural Research and Development Center (OARDC), 305 Gerlaugh Hall, 1680 Madison Avenue, 44691, Wooster, OH, USA aut Agu Chidozie Department of Animal Sciences, The Ohio State University, and Ohio State Agricultural Research and Development Center (OARDC), 305 Gerlaugh Hall, 1680 Madison Avenue, 44691, Wooster, OH, USA aut Gopalan Venkat Department of Chemistry and Biochemistry, and Center for RNA Biology, The Ohio State University, 484 West 12th Avenue, 43210, Columbus, OH, USA aut Ezeji Thaddeus Department of Animal Sciences, The Ohio State University, and Ohio State Agricultural Research and Development Center (OARDC), 305 Gerlaugh Hall, 1680 Madison Avenue, 44691, Wooster, OH, USA aut Applied Microbiology and Biotechnology Springer Berlin Heidelberg 99/8(2015-04-01), 3729-3740 0175-7598 99:8<3729 2015 99 253 https://doi.org/10.1007/s00253-015-6450-3 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00253-015-6450-3 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Ujor Victor Department of Animal Sciences, The Ohio State University, and Ohio State Agricultural Research and Development Center (OARDC), 305 Gerlaugh Hall, 1680 Madison Avenue, 44691, Wooster, OH, USA aut NATIONALLICENCE 700 1- Agu Chidozie Department of Animal Sciences, The Ohio State University, and Ohio State Agricultural Research and Development Center (OARDC), 305 Gerlaugh Hall, 1680 Madison Avenue, 44691, Wooster, OH, USA aut NATIONALLICENCE 700 1- Gopalan Venkat Department of Chemistry and Biochemistry, and Center for RNA Biology, The Ohio State University, 484 West 12th Avenue, 43210, Columbus, OH, USA aut NATIONALLICENCE 700 1- Ezeji Thaddeus Department of Animal Sciences, The Ohio State University, and Ohio State Agricultural Research and Development Center (OARDC), 305 Gerlaugh Hall, 1680 Madison Avenue, 44691, Wooster, OH, USA aut NATIONALLICENCE 773 0- Applied Microbiology and Biotechnology Springer Berlin Heidelberg 99/8(2015-04-01), 3729-3740 0175-7598 99:8<3729 2015 99 253