Microbial production of organic acids: expanding the markets Michael Sauer 1, 2 , Danilo Porro 3 , Diethard Mattanovich 1, 2 and Paola Branduardi 3 1 School of Bioengineering, FH Campus Wien – University of Applied Sciences, Muthgasse 18, 1190 Wien, Austria 2 Institute of Applied Microbiology, Department of Biotechnology, BOKU – University of Natural Resources and Applied Life Sciences, Muthgasse 18, 1190 Wien, Austria 3 Department of Biotechnology and Biosciences, University of Milan-Bicocca, Piazza della Scienza 2, 20126 Milan, Italy Microbial production of organic acids is a promising approach for obtaining building-block chemicals from renewable carbon sources. Although some acids have been produced for some time and in-depth knowledge of these microbial production processes has been gained, further microbial production processes seem to be feas- ible, but large-scale production has not yet been possible. Citric, lactic and succinic acid production exem- plify three processes in different stages of industrial development. Although the questions being addressed by current research on these processes are diverging, a comparison is helpful for understanding microbial organic acid production in general. In this article, through analysis of the current advances in production of these acids, we present guidelines for future devel- opments in this fast-moving field. Introduction: organic acids as building-block chemicals A major step for the development of a sustainable, indus- trial society will be the shift from our dependence on petroleum to the use of renewable resources. Bio-refineries enable production of bio-fuels as well as building-block chemicals from biomass as outlined in Box 1. The market share of biotechnological processes for the production of various chemical products is expected to rise from the current level of 5% to 20% by 2010 [1]. In the long run, the use of petroleum could be eliminated and greenhouse gas emissions reduced. These processes are also favorable from a chemical and economic point of view. Functional groups that must be introduced by costly oxidative process steps into naphta are already present in plant materials such as carbohydrates. Organic acids constitute a key group among the building-block chemicals that can be produced by microbial processes (Table 1). Most of them are natural products of microorganisms, or at least natural intermediates in major metabolic pathways. Because of their functional groups, organic acids are extremely useful as starting materials for the chemical industry as outlined for succinic acid in Box 2. It is noteworthy that for many organic acids the actual market is small, but an economical production process will create new markets by providing new opportunities for the chemical industry. For example, succinic, fumaric and malic acid could replace the petroleum-derived commodity chemical maleic anhydride. The market for maleic anhydride is huge, whereas the current market for the organic acids mentioned is small owing to price limitations. Once a competitive microbial production process for one of these acids is established the market for that acid will increase [2]. Consequently, the field that investigates microbial organic acid production is currently moving fast. Here, we summarize the recent developments exemplified by three products: citric acid, which has been on the market for some time, lactic acid, which came to market in large- scale only recently, and succinic acid, which (despite the fact that a feasible industrial bio-process has not yet been developed) has huge potential as a building-block chemical (see Table 2 for an overview of data from scientific litera- ture). Trends in the field are seen (see below) but, because of the sensitivity of the data between industrial competitors, few process details are known, which impedes sound techno-economic evaluations. Consequently, this review is based on the available scientific literature, which does not entirely reflect the needs of the industry or the current status of ongoing studies. Nevertheless, we set the current trends in academia in context with industrial needs as far as information is available. Microbial organic acid production: three acids as examples From Italian lemons to filamentous fungi: citric acid The oldest microbial process for production of a high- volume, low cost organic acid is the production of citric acid by the filamentous fungus Aspergillus niger. Currently the yearly production of citric acid is approximately 1.6 million tons (t) [3]. Unlike most of the other bio-derived acids that are considered industrial products, citric acid was produced industrially before the development of a microbial process. The industrial production relied on extraction from Italian lemons until it was discovered that Aspergilli accumulate this acid in high amounts under certain conditions (reviewed by Papagianni [4]). The cru- cial parameters resulting in efficient production of citric acid by A. niger have been determined empirically and include high substrate concentration, low and finite content of nitrogen and certain trace metals, thorough maintenance of high dissolved oxygen, and low pH. The exact definition of these parameters enabled the development of highly efficient biotechnological processes. However, many of the biochemical and physiological mechanisms underlying Review Corresponding author: Sauer, M. (michael.sauer@fh-campuswien.ac.at). 100 0167-7799/$ – see front matter ß 2007 Elsevier Ltd. All rights reserved. doi:10.1016/j.tibtech.2007.11.006 Available online 11 January 2008