ORIGINAL ARTICLE A comparative study of Taxol production in liquid and solid-state fermentation with Nigrospora sp. a fungus isolated from Taxus globosa J. Ruiz-Sanchez 1 *, Z.R. Flores-Bustamante 1 *, L. Dendooven 1 , E. Favela-Torres 2 , G. Soca-Chafre 1 , J. Galindez-Mayer 3 and L.B. Flores-Cotera 1 1 Cinvestav-IPN, Department of Biotechnology and Bioengineering, Av. Instituto Polite ´ cnico Nacional 2508, Me ´ xico, D.F., Me ´ xico 2 Universidad Auto ´ noma Metropolitana (UAM-Iztapalapa), Department of Biotechnology, Av. San Rafael Atlixco 186, Me ´ xico, D.F., Me ´ xico 3 Escuela Nacional de Ciencias Biolo ´ gicas-IPN, Department of Biochemical Engineering, Av. Carpio y Plan de Ayala, Me ´ xico, D.F., Me ´ xico Introduction Taxol is an oxygenated diterpene produced by different species of yew trees (Taxus sp.), with important appli- cations as anticancer agent. Originally, Taxol was obtained from the bark of yew trees, but several other alternatives have been developed during the past 20 years, including total synthesis (Holton et al. 1994; Nicolaou et al. 1994), semisynthesis (Patel 1998; Baloglu and Kingston 1999), cell culture (Kim et al. 2004; Ta- bata 2004; Khosroushahi et al. 2006) and fermentation with endophytic fungi (Stierle et al. 1993; Strobel et al. 1996). In spite of considerable progress in production techniques, Taxol is still a high-priced drug, conse- quently out of reach for many people in the world. New approaches and further improvement of estab- lished production technology are needed to reduce the cost of Taxol production. Taxol has been detected in more than 30 unrelated fungal endophytes including the genera Pestalotia, Pestal- otiopsis, Fusarium, Alternaria, Pithomyces, Monochaetia, Penicillum, Truncatella, Tubercularia, Sporormia, Tricho- thecium and Seimatoantlerium (Strobel et al. 1996; Wang et al. 2000; Shrestha et al. 2001). Fungi have a consid- erable potential to be used in economical and environ- mentally friendly fermentation processes for Taxol production. They grow fast in simple culture media, can be manipulated easily and cultured on large scale. Conse- quently, fungi could provide a reliable source of Taxol through fermentation. However, little is known about Keywords endophytic, medium concentration, Mexican yew, paclitaxel. Correspondence Luis B. Flores-Cotera, Cinvestav-IPN, Department of Biotechnology and Bioengineering, Av. Instituto Polite ´ cnico Nacional 2508, Col. San Pedro Zacatenco, Me ´ xico 07360, D.F., Me ´ xico. E-mail: lfcotera@cinvestav.mx *These co-authors contributed equally to this work. 2009 ⁄ 1909: received 23 March 2010, revised 6 July 2010 and accepted 11 August 2010 doi:10.1111/j.1365-2672.2010.04846.x Abstract Aims: To determine in liquid (LF) and solid-state fermentation (SSF) the effect of medium concentration on growth and Taxol produced by Nigrospora sp., a fungus isolated from the Mexican yew. Methods and Results: Nigrospora sp. was grown at different concentrations of the base culture medium M1D, i.e. two (2·), four (4·), six (6·) and eight times (8·) the base concentration. The titres of Taxol determined by competi- tive inhibition enzyme immunoassay increased with increasing medium concentration in LF and SSF but were higher in SSF in every medium concen- tration. The Taxol produced in SSF and LF with 8· medium was 221 and 142 ng l )1 . The SSF gave also higher biomass, growth and sugar utilization than LF in every medium. The growth and sugar consumption were modelled by the logistic and the Pirt models, respectively. However, the Luedeking–Piret model was unsuitable for Taxol. Conclusions: The SSF surpassed LF in terms of Taxol, growth and sugar utili- zation; thus, it has significant advantages over LF. Significance and Impact of the Study: This is the first report on Taxol produc- tion by SSF and the first contribution to evaluate the influence of the medium on Taxol production in LF and SSF. Journal of Applied Microbiology ISSN 1364-5072 2144 Journal of Applied Microbiology 109, 2144–2150 ª 2010 The Society for Applied Microbiology ª 2010 The Authors