Published: June 30, 2011 r2011 American Chemical Society 1690 dx.doi.org/10.1021/ie200879s | Ind. Eng. Chem. Res. 2012, 51, 1690–1696 ARTICLE pubs.acs.org/IECR Synergistic Optimal Integration of Continuous and Fed-Batch Reactors for Enhanced Productivity of Lignocellulosic Bioethanol Hyun-Seob Song, Seung Jin Kim, and Doraiswami Ramkrishna* School of Chemical Engineering, Purdue University, West Lafayette, Indiana 47907, United States ABSTRACT: With significant technological advances in metabolic engineering, there are currently available efficient recombinant yeast strains capable of fermenting lignocellulosic sugars (i.e., glucose and xylose) to bioethanol. Conventional batch fermentation, preferred in most bioprocesses, may not provide the most appropriate environments for those engineered strains to perform their best. In this article, we consider new reactor configurations integrating different types of reactors to examine their maximal productivity of lignocellulosic bioethanol. Among various possible scenarios, the highest performance was acquired from a synergistic operation of continuous and fed-batch reactors. In a chemostat, glucose is fermented alone by the hexose-only fermenting (wild-type) yeast, and unconverted xylose is fed to a batch reactor where mixed sugars are fermented by recombinant yeast. The optimization of the feed rate is a critical issue in order to maximize the productivity in a fed-batch reactor. It is shown that the proposed idea is able to increase the bioethanol productivity by up to 50% in comparison to a simple batch operation. Obviously, these considerations must be integrated with a more comprehensive costÀbenefit analysis before a clear choice of reactor configuration can emerge. 1. INTRODUCTION We are pleased to contribute to the special issue in honor of Professor K. D. P. Nigam, who has made lasting contributions to Chemical Reaction Engineering. Our article addressing reactor configurations to improve bioethanol productivity is hopefully a fitting tribute to Professor Nigam with respect to his focus on process intensification. The production of bioethanol has an old history. It had been used, for example, as a transportation fuel in Germany and France, and as a fuel in Brazil and United States as well as in Europe, already during the late 19th and early 20th centuries. 1 After the oil crisis in the 1970s, current interest in bioethanol is even greater due to not only depletion of the oil reserves but also the negative impact of fossil fuels on the environment such as high greenhouse gas emissions. Production of bioethanol as an alternative to petroleum-based liquid fuels has increased over the last several decades, in particular rapidly from 2000. 2 The bulk of currently used bioethanol is produced from sucrose-containing feedstocks (e.g., sugar cane) or starch-based materials (e.g., corn, wheat and barley). The use of these first generation feedstocks is not considered sustainable because of several issues such as food-fuel conflict and their limited avail- ability relying on geographic locations and seasons. The second generation feedstock, which can serve as a renewable resource for bioethanol production, is lignocellulosic biomass such as rice straw, 3 wheat straw, 2 corn stover, 4 switchgrass, 5 and various other agriculture and forest residues. Lignocelluose is mainly composed of cellulose, hemicelluloses, and lignin. Through the pretreatment and hydrolysis steps, they are broken down to release a wide spectrum of sugars with six (hexoses) and five car- bons (pentoses). Bioethanol is finally obtained via fermention of those mixed sugars. The lignocellulosic bioethanol is, however, not at the stage of commercial production for which it is essential to reduce the production cost in all possible steps throughout biomass-to-bioethanol processes. Our objective in this paper is to seek ways to increase the productivity of lignocelluosic ethanol at the fermentation step. Traditionally, the yeast Saccharomyces cerevisiae has been used for industrial bioethanol production from crop-based feedstocks. The same strain is not suitable, however, for fermenting cellulosic sugars containing pentoses (i.e., xylose) as well as hexoses (i.e., glucose). This is because the wild-type S. cerevisiae can ferment glucose but hardly xylose, the second most abundant sugar (next to glucose) in the spectrum of cellulosic sugars. Various meta- bolic engineering attempts have been made to push and pull xy- lose into the central metabolism of S. cerevisiae. 6,7 Push strategies include introduction of xylose transport and its initial metabolic routes (e.g., by expressing heterologous genes encoding xylose reductase and xylitol dehydrogenase), while pull strategies include overexpression of xylulose kinase and/or other enzymes of pen- tose phosphate pathways. Consequently, a number of recombinant yeast strains cofermenting glucose and xylose are now available. 6 The productivity of ethanol is affected by cultivation methods as well as fermenting organisms. Batch reactors are most com- monly used in industry, although fed-batch and modified forms of continuous systems are also considered. 8 The suitable choice of reactors should be made considering the substrate type and traits of fermenting organisms, as well as economic aspects. This is a practically important subject that has not been investigated in detail in regard to lignocellulosic bioethanol. Special Issue: Nigam Issue Received: April 22, 2011 Accepted: June 30, 2011 Revised: June 29, 2011