576 Korean J. Chem. Eng., 27(2), 576-586 (2010) DOI: 10.1007/s11814-010-0101-2 RAPID COMMUNICATION † To whom correspondence should be addressed. E-mail: ramkrish@ecn.purdue.edu ‡ This paper is dedicated to Professor Jae Chun Hyun for celebrating his retirement from Department of Chemical and Biological Engineer- ing of Korea University. Issues with increasing bioethanol productivity: A model directed study Hyun-Seob Song and Doraiswami Ramkrishna † School of Chemical Engineering, Purdue University, West Lafayette, IN 47907 (Received 3 September 2009  accepted 31 October 2009) Abstract −We explore a way to improve the efficiency of fermentation of lignocellulosic sugars (i.e., glucose and xylose) to bioethanol in a bioreactor. For this purpose, we employ the hybrid cybernetic model developed by Song et al. (Biotechnol and Bioeng, 103: 984-1000, 2009), which provides an accurate description on metabolism of recombi- nant S. cerevisiae due to its unique feature of accounting for cellular regulation. A comprehensive analysis of the model reveals many interesting features of the process whose balance is critical for increasing the productivity of bioethanol. In particular, the addition of extra xylose to the medium may increase ethanol productivity (a somewhat counterintui- tive result as xylose metabolism is slower!), but one that must be orchestrated with control of other important variables. Effects of xylose addition are shown to be different for different reactor environments. In a batch culture, xylose addi- tion substantially improves ethanol productivity at low sugar concentration (e.g., about 45% up by increasing initial xylose concentration from 10 to 30 g/L with glucose concentration of 20 g/L), but worsens it at high sugar concentration (e.g., about 10% drop by increasing xylose concentration from 40 to 160 g/L with glucose concentration of 80 g/L). On the other hand, the productivity of chemostats is constantly improved by increasing the ratio of xylose to glucose level in the feed. It is found that multiple local maxima can exist in chemostats and, consequently, optimal composition for mixed sugars is different depending on the allowable range of xylose addition. Batch operation, however, is found to be superior when mixed sugars are consumed slowly, while continuous operation becomes attractive for rapidly me- tabolized sugars such as pure glucose. Optimal reactor configurations for given lignocellulosic sugars are shown to depend on calculated operating curves. Reasonably close comparison of model simulations with existing batch fer- mentation data provides support in part to the value of the current effort. The lesson that emerges is the importance of modeling in improving the efficiency of bioprocesses. Key words: Bioethanol Productivity, Hybrid Cybernetic Model, Optimization, Sugar Composition, Recombinant S. cerevisiae INTRODUCTION Concerns about climate change, high oil price, and peak oil have revived worldwide interest in renewable energy to supplement fos- sil fuels. The forecast of 50% increase in the world energy con- sumption over the next two decades [1] with its doubling between 2000 and 2050 [2] has greatly enhanced the need for diversifying energy sources. Among various renewable energy technologies cur- rently available, particular attention has been paid to converting bio- mass to bioethanol (and biodiesel) for use in the transportation sector which accounts for more than two-thirds of the total liquid fuel con- sumption [1]. The production of bioethanol from plant biomass is not a new concept, as it has been available on a large scale since the first energy crisis in 1973 using crops such as sugar cane, sugar beet, corn and cereals [3]. Unfortunately, the significant use of such crop-derived biofuels creates the so-called ‘food-or-fuel debate’ due to the com- petition with food for the feedstock and agricultural lands. This di- lemma could be remedied by utilizing lignocelluosic biomass such as forestry (wood, grasses), agricultural (corn stalks, wheat straw, sugar cane bagasse), industrial (waste from pulp and paper industry), and urban residues (municipal solid waste). Lignocellulose is a complex substrate, consisting of three major components: cellulose (33-51%), hemicelluose (19-34%) and lignin (20-30%) [4,5]. Cellulose is a homopolymer of glucose, while hemi- cellose is a heteropolymer composed of hexose (glucose, mannose, and galactose) and pentose sugars (xylose and arabinose). Lignin does not contain carbon sources but provides rigidity to the struc- ture. In a typical composition of common lignocelluosic biomass, glucose (30-40%) and xylose (10-20%) are the most predominant sugars, while the relative portion of the (hemicellose) constituents varies depending on the plant source [4,6]. Lignocellulosic feed- stock is first converted to sugars through pretreatment and hydrolysis, followed by fermentation finally to ethanol. Traditionally, Saccharo- myces cerevisiae has been used for sugar- and starch-based ethanol production, but the same strain is not suitable for converting ligno- cellulosic sugars since it only ferments glucose (the most dominant), but cannot xylose (the next abundant). Thus, considerable efforts have been made to endow S. cerevisiae with the ability to utilize xylose as well as glucose through metabolic engineering [7]. The overall diagram of so-called B2B (biomass to biofuel) process is illustrated in Fig. 1. Cost-benefit analysis of the ethanolic fermentation process reveals that the processing cost is more dominant (two-thirds of the total cost) than the feed cost [8,9]. It is thus considered important to in- crease the processing efficiency, not just the sugar conversion alone.