IOSR Journal of Pharmacy and Biological Sciences (IOSR-JPBS) e-ISSN: 2278-3008, p-ISSN:2319-7676. Volume 8, Issue 3 (Nov. – Dec. 2013), PP 49-59 www.iosrjournals.org www.iosrjournals.org 49 | Page Bioprocess Development for High Cell Mass Production of the Probiotic Yeast-Kluyveromyces lactis Hun C.H 1 , Mohd Sueb M.S. 1,2 , Abd Malek R. 1 , Othman Z. 1 , Elsayed E.A. 3,4 , Ramili, S. 1 , Elmarzugi N.A. 1,6 , Sarmidi M.R. 1 , Aziz R. 1 , El Enshasy H.A. 1,5* 1 Institute of Bioproduct Development, Universiti Teknologi Malaysia, 81310 Skudai Johor, Malaysia. 2 Faculty of Chemical Engineering & Natural Resources, Universiti Malaysia Pahang, Lebuh Raya Tun Razak, 26300 Gambang, Kuantan, Pahang, Malaysia. 3 Bioproducts Research Chair, Zoology Department, Faculty of Science, King Saud University, Riyadh, Saudi Arabia. 4 Natural and Microbial Products Department, National Research Centre, Dokki, Cairo, Egypt 5 Bioprocess Development Department, City for Scientific Research and Technology Applications (CSAT), New Burg Al Arab, Alexandria, Egypt. 6 Dept. of Industrial Pharmacy, Faculty of Pharmacy/ Tripoli University& Biotechnology Research Center, NASR, Libya. Abstract : In the present study, the key industrial strain of Kluyveromyces lactis NRRL Y-110 was used to develop an industrial process for probiotic cell mass production. Therefore, the biomass production process of K. lactis was developed via the optimization of different medium and process parameters in shake flask and bioreactor levels. In the first part of the work, the effect of medium composition on the production of biomass was investigated in shake flask culture. Among different production media studied, the medium composed of lactose, ammonium sulphate, magnesium sulphate, potassium dihydrogen phosphate and yeast extract yielded the highest volumetric high cell mass production of 4.34 g.L -1 after 24 hours cultivation. Furthermore, the optimization involved different key nutrients (carbon sources, nitrogen sources and mineral sources). The results obtained are helpful for the overproduction of highest cell mass by submerged culture of K. lactis on a semi-industrial scale. During bioreactor cultivation under controlled and uncontrolled pH, results showed that, high cell biomass yield of 15.1 g.L -1 was produced under controlled pH conditions compared to uncontrolled pH. This value was almost 48.30% higher than those obtained in controlled pH submerged shake flask culture. Keywords: Kluyveromyces lactis, Probiotic, Biomass Production, Bioprocess optimization I. INTRODUCTION Probiotics are viable microorganism or microbial mixtures which are able to colonize in the intestine and are administrated to improve the human body microbial balance by producing certain beneficial metabolites and to compete other pathogenic microorganisms. Therefore, they are considered as one of the main wellness products of growing interest in different countries [1]. For many years, most of research in this field was focused mainly on the isolation, biomass production and application of different bacterial probiotics especially those belonging to Lactobacilli such as L. lactis [2], L. salivarius [3], L. delbrueckii [4] and L. plantarum [5]. In addition to bacteria, different types of yeast strains were also proved to have probiotic/biotherapeutic activity when applied as single culture or in addition to other probiotic strains. These yeast strains are mainly: Saccharomyces cerevisia, S. boulardii , and Kluyveromyces lactis. Therefore, special interest was paid recently on research related to biomass production of probiotic yeasts in semi-industrial and industrial scales [6-8]. Kluyveromyces lactis is a yeast strain used in different industrial and research applications [9,10]. The name of this yeast was derived from its capability to assimilate lactose and its conversion into lactic acid. With the GRAS status given by the Food and Drug Administration (FDA), K. lactis has been known as a normal, even necessary component of many cultured dairy products” and yet “no reports of toxicity or pathogenicity have ever been associated with the presence of K. lactis has been reported in food [10,11]. Many studies had been done on the wide applications of K. lactis in industries. According to Van Ooyen et al [9], K. lactis acts as an excellent host for recombinant chymosin production in large scale, which was the first protein from higher eukaryote origin to be expressed in single cellular organisms. Merico et al. [12] have also reported that K. lactis is commercially used to produce lactase- and lactose-free milk and is also considered as a potential source for the production of α-galactosidase in food industry. In one report stated by Swinkels et al. [13], genetically modified K.lactis has been used to produce human serum albumin, human interleukin-1 beta, and hepatitis B surface antigen and other important biopharmaceuticals. Therefore, from an industrial point of view, the yeast biomass is a one fascinating raw material, having wide benefits and application which could be utilized in the production of foods, feeds, biochemical, etc. As being regarded as non-conventional yeast, scientific researches