Kinetic modeling and scale up of lipoic acid (LA) production from Saccharomyces cerevisiae in a stirred tank bioreactor

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ORIGINAL PAPER

Kinetic modeling and scale up of lipoic acid (LA) production from Saccharomyces cerevisiae in a stirred tank bioreactor Shilpa S. Jayakar • Rekha S. Singhal

Received: 30 April 2012 / Accepted: 31 October 2012 / Published online: 24 November 2012 Ó Springer-Verlag Berlin Heidelberg 2012

Abstract Scale up studies for production of lipoic acid (LA) from Saccharomyces cerevisiae have been reported in this paper for the first time. LA production in batch mode was carried out in a stirred tank bioreactor at varying agitation and aeration with maximum LA production of 512 mg/L obtained at 350 rpm and 25 % dissolved oxygen in batch culture conditions. Thus, LA production increased from 352 mg/L in shake flask to 512 mg/L in batch mode in a 5 L stirred tank bioreactor. Biomass production under these conditions was mathematically explained using logistic equation and data obtained for LA production and substrate utilization were successfully fitted using Luedeking–Piret and Mercier’s models. The kinetic studies showed LA production to be growth associated. Further enhancement of LA production was carried out using fedbatch (variable volume) and semi-continuous modes of fermentation. Semi-continuous fermentation with three feeding cycles of sucrose effectively increased the production of LA from 512 to 725 mg/L. Keywords Lipoic acid (LA)  Saccharomyces cerevisiae  Stirred tank bioreactor  Kinetic modeling  Semi-continuous fermentation

Electronic supplementary material The online version of this article (doi:10.1007/s00449-012-0859-1) contains supplementary material, which is available to authorized users. S. S. Jayakar (&)  R. S. Singhal Food Engineering and Technology Department, Institute of Chemical Technology (Deemed University), Matunga, Mumbai 400 019, India e-mail: [email protected] R. S. Singhal e-mail: [email protected]

Introduction Lipoic acid (LA) also known as 6,8-thioctic acid, 1,2dithiolane-3-pentanoic acid is a naturally occurring cofactor reported to be present in a diverse group of microorganisms, plant and animal tissues [1]. It is an essential cofactor required for functioning of pyruvate dehydrogenase, a-ketoglutarate dehydrogenase and glycine cleavage enzyme complexes in eukaryotes and bacteria and has the capacity to regenerate other antioxidants such as glutathione, vitamin C and E [2, 3]. It is used in therapies for certain diseases accompanied by oxidative stress such as diabetes, atherosclerosis, neurodegenerative diseases, and acquired immune deficiency syndrome (AIDS) [4]. LA has been used as a potent antioxidant, as a detoxication agent for heavy metal poisoning, and has been implicated as a means to improve age-associated cognitive decline [5]. It is synthesized de novo in mitochondria by LA synthase and is derived from octanoic acid [5, 6]. A number of microorganisms such as Escherichia coli, Bacteroides fragilis, Aerobacter aerogenes, Azotobacter vinelandii, Bacillus subtilis, Micrococcus lysodeikticus, Saccharomyces cerevisiae, Pseudomonas reptilivora, an