Appl Microbiol Biotechnol (2010) 85:893–899 DOI 10.1007/s00253-009-2262-7 MINI-REVIEW Pentanol isomer synthesis in engineered microorganisms Anthony F. Cann & James C. Liao Received: 7 July 2009 / Revised: 11 September 2009 / Accepted: 11 September 2009 / Published online: 27 October 2009 # The Author(s) 2009. This article is published with open access at Springerlink.com Abstract Pentanol isomers such as 2-methyl-1-butanol and 3-methyl-1-butanol are a useful class of chemicals with a potential application as biofuels. They are found as natural by- products of microbial fermentations from amino acid sub- strates. However, the production titer and yield of the natural processes are too low to be considered for practical applica- tions. Through metabolic engineering, microbial strains for the production of these isomers have been developed, as well as that for 1-pentanol and pentenol. Although the current production levels are still too low for immediate industrial applications, the approach holds significant promise for major breakthroughs in production efficiency. Keywords Pentanol . 2-Methyl-1-butanol . 3-Methyl-1-butanol . Biofuels Introduction Modern society relies heavily on energy, especially the energy required for the transportation of goods, services, and people. For the past century, most of our transportation energy has come from fuels derived from petroleum. However, petroleum is a non-renewable resource, and recent efforts have pushed for alternatives. A heavily pro- duced alternative to gasoline is ethanol primarily because ethanol production is a long-established art. Yet as a fuel, ethanol does not compare well to gasoline because it has a much lower energy density (only 21 MJ/L versus about A. F. Cann : J. C. Liao (*) Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, CA 90095, USA e-mail: liaoj@ucla.edu 32 MJ/L for gasoline) and a high hygroscopicity. Pentanol isomers, as well as other higher alcohols, have a low affinity for water and an energy density of about 28 MJ/L and fit well into the current transportation infrastructure. Beyond their potential use as fuel, pentanol isomers also have a multitude of other applications. Several reviews about microbial production of biofuels in general have been written in the past 2 years (Antizar- Ladislao and Turrion-Gomez 2008; Atsumi and Liao 2008; Fortman et al. 2008; Connor and Liao 2009). These reviews address a wide range of topics but are limited in their discussion about the exciting new research on pentanol production. In this paper, we take a more in-depth look at the pentanols: how they are biologically produced, how that can be improved upon, and what applications they can serve. Natural production of pentanols Pentanols, or amyl alcohols, have long been known to the food industry as one of many flavor compounds produced during fermentation. Studies have shown pentanols, along with their related aldehydes, acids, and esters, to be the most abundant odor and flavor components of fermented beverages (Soccol et al. 2007). In particular, 3-methyl-1-butanol (isoamyl alcohol) is often the main fermentation flavor compound after ethanol (Lurton et al. 1995; Boulton et al. 1996). Initially, the focus was on how these compounds affected the taste of fermented food products, but eventually, more research was conducted to determine the mechanism for their production. In the beginning of the twentieth century, Ehrlich (1907) first discovered the connection between certain amino acids and the presence of higher alcohols in beer. Ehrlich’s work led to the discovery of the eponymous pathway and decades of research (Sentheshanuganathan 1960; Dickinson et al.