(365a) Quantitative Structure-Activity Relationship (QSAR) Study on Carbonyl Inhibition of Microbial Fermentation

Tu, M., Auburn University
Cao, D., Auburn University
Xie, R., Auburn University

Biomass pretreatment generates significant amount of fermentation inhibitors from the degradation of cellulose, hemicellulose, lignin and extractives. Significant efforts have been made to identify inhibitors in biomass hydrolysates using analytical separation and identification tools including HPLC, GC/MS, LC/MS and NMR. Understanding of the potent inhibitors that have the most pronounced effects on microbial fermentation is yet to be established. Most currently identified inhibitors all have a functional carbonyl group (C=O).

Carbonyl compounds are reactive: the positive charge of carbon can initiate a nucleophilic addition between nucleophiles and electrophiles. Consequently, the inhibitory effects of carbonyl compounds are governed by their electrophilic reactivity towards biological nucleophiles. The objective of this study was to identify the specific molecular descriptors that correlate molecular structure of carbonyls to their inhibitory activity. Quantitative structure-activity relationship (QSAR) modeling was used in assessing the reactivity of carbonyls. Molecular descriptors that were studied in this work included hydrophobicity (Log P),  dipole moment, energy of the lowest unoccupied molecular orbital (ELUMO), energy of the highest occupied molecular orbital (EHOMO) and electrophilicity index (ω).

The quantitative information on carbonyl inhibition was evaluated based on the glucose initial consumption rate and the final alcohol yield. We identified that ELUMO is a very good global parameter to correlate the molecular structure of carbonyl compounds to their inhibitory effects. The alcohol dehydrogenase (ADH) activity in response to vanillin inhibition was determined from the batch fermentation results. Effects of acetic acid and benzoic acid on alcoholic fermentation were also studied with and without pH control. Using those data, the correlation between fermentation inhibition and carbonyl molecular descriptors were established.