BIOTECHNOLOGICAL PRODUCTS AND PROCESS ENGINEERING Elicitation of Streptomyces coelicolor with dead cells of Bacillus subtilis and Staphylococcus aureus in a bioreactor increases production of undecylprodigiosin Khalid Jaber Kadhum Luti & Ferda Mavituna Received: 8 September 2010 / Revised: 20 November 2010 / Accepted: 23 November 2010 / Published online: 14 December 2010 # Springer-Verlag 2010 AbstractSince microorganisms normally co-exist with other species in nature, they have developed complex metabolic and physiological responses as a resultof such interspecies interactions. Weutilized someof theseinteractions by introducing heat-killed cells of Bacillus subtilis and Staphy- lococcus aureus to Streptomyces coelicolor cultures and, as a result, stimulated undecylprodigiosin production. Undecyl- prodigiosin isnot only an antibiotic; it has also been attributedwith antitumoractivities,but,in a defined medium, pure cultures of S. coelicolor produced only low concentrations. Elicitation with B.subtilisincreased the maximum undecylprodigiosin concentration by threefold and S.aureus by fivefold compared with the pure culture of S. coelicolor. Growth and glucose consumption of elicited S. coelicolor, however, remained similar to those observed in the pure culture. Furthermore, another positive outcome of the elicitation with both B. subtilis and S. aureus was the earlieronsetof undecylprodigiosin production by 24 h compared with the pure culture of S. coelicolor. This is the first time that such a phenomenon has been seen in 2L bioreactors. Our work supports the use of biotic elicitation in order to enhance the production of secondary metabolites for industrial-scale applications. Keywords Streptomyces coelicolor . Bacillus subtilis . Staphylococcus aureus . Elicitation . Undecylprodigiosin . Bioreactor Introduction Undecylprodigiosin is one of the antibiotics produced by Streptomyces coelicolor.It belongsto the family of prodiginines that are a group of tripyrrole red pigments. Undecylprodigiosin is chemically similar to prodigiosin produced by Serratia marcescens, both having straight- chain alkylsubstituents in pyrrole C,in prodigiosin, a methylgroup atC-2 and a pentyl group atC-3 and in undecylprodigiosin, undecylside-chain atposition C-2 (Williamson etal. 2006).It is thoughthatboth com- pounds have a similar biosynthesis pathway (White and Bibb 1997). During thelast two decades, this antibioticgained importance and became an attractive research topic due t its immunosuppressive and anticancer properties, in addi- tion to antimicrobial activities (Williamson et al. 2006). Indeed, the selective apoptotic effect of undecylprodigiosi on breast carcinoma cells designated it as a novel antican drug forthe treatment of breastcancer(Ho etal. 2007). Differentmethodshavebeen used formaximizing the productivity ofprodigiosin from S. marcescens. These methods focused, in general, on the improvement of the fermentation medium andoptimizationof the culture conditions (Rjazantseva et al. 1994). Furthermore, selectiv amino acids(Weiet al. 2005),sodium dodecyl sulfate (Feng et al. 1982), and some vegetable oils (Wei and Chen 2005) were used successfully to enhance the production o prodigiosin from S. marcescens. In nature,microorganisms exist in complexmixed populations. Some ofthe microbial interactions in these populations are thought to be the driving force for the production of mostsecondary metabolites such as anti- biotics(Oh et al. 2005).Elicitation can simulate some aspectsof such interspecies interactions. In its general K. J. K. Luti : F. Mavituna (*) School of Chemical Engineering and Analytical Science, The University of Manchester, Oxford Road, Manchester M13 9PL, UK e-mail: ferda.mavituna@manchester.ac.uk Appl Microbiol Biotechnol (2011) 90:461–466 DOI 10.1007/s00253-010-3032-2