A novel finding thatStreptomyces clavuligeruscan produce the antibiotic clavulanic acid using olive oil as a sole carbon source

Abstract

Aims: This study aims to establish whether commercially available food oils can be used by Streptomyces clavuligerus as sole carbon sources for growth and clavulanic acid production. Methods and results: Batch cultures in bioreactors showed that Strep. clavuligerus growth and clavulanic acid yields in a P‐limited medium containing 0.6% (v/v) olive oil were respectively 2.5‐ and 2.6‐fold higher than in a glycerol‐containing medium used as control. Glycerol‐ and olive oil‐grown cells present different macromolecular composition, particularly lipid and protein content. Conclusions: Streptomyces clavuligerus uses olive oil as the sole carbon and energy source for growth and clavulanic acid production. Yields and production rates in olive oil are comparable to those reported for oil‐containing complex media. Differences in yields and in the macromolecular composition indicate that different metabolic pathways convert substrate into product. Significance and impact of the study: This is the first report of oils being used as the sole carbon source by Strep. clavuligerus. Apart from economic benefits, interesting questions are raised about Strep. clavuligerus physiology. Defined culture media allow physiological studies to be performed in the absence of interference by other compounds. Understanding how Strep. clavuligerus catabolises oils may have an economic impact in clavulanic acid production.

Fermentation Conditions that Affect Clavulanic Acid Production in Streptomyces clavuligerus: A Systematic Review

“…Different vegetable oils may stimulate the production of clavulanic acid, as demonstrated by two different studies. In batch fermentation, Efthimiou et al ( 2008 ) described increased clavulanic acid production when olive oil was used in place of glycerol as a sole carbon source; with a maximum concentration of 47 mg/L being recorded, which is nearly double that observed in media containing glycerol (25 mg/L). These results were consistent with another recent study, whereby the addition of olive oil improved clavulanic acid production as compared to glycerol; with a maximum concentration at 1120 and 564 mg/L, respectively (Salem-Berkhit et al, 2010 ).…”

“…Based on literature obtained in this study, glycerol was found to be the most popular choice of carbon source in clavulanic acid production; in order to ensure an efficient supply of glyceraldehyde-3-phosphate Once glycerol is metabolized into glyceraldehyde-3-phosphate, it can either enter the clavulanic acid biosynthesis pathway, or be involved in glycolytic or gluconeogenesis reactions (Figure 3 ). The inclusion of glycerol enhances the production of clavulanic acid as compared to carbohydrates, as glycerol provides a higher energy content on a weight-by weight basis (Efthimiou et al, 2008 ). As glycerol serves as a backbone for triglycerides, its utilization by S. clavuligerus has prompted researchers to study the potential of other oils to be used as a source of carbon.…”

Production of β-Lactamase Inhibitors by Streptomyces Species

“…Oils are preferred in terms of energy, as they contain approximately 2.4 times the energy of glucose [ 57 ]. Several authors have reported that oils may stimulate CA production [ 93 , 99 , 109 , 110 , 111 , 112 , 113 ]. Lee and Ho [ 109 ] identified palm and palm-kernel oils as the most suitable carbon sources for growth of S. clavuligerus and CA production.…”

“…Efthimiou et al [ 112 ] described an increase in CA production when 47 mg/L olive oil was used instead of 25 mg/L glycerol as the sole carbon source. In a similar study on the effects of different vegetable oil-based media on cell growth and CA production during S. clavuligerus ATCC 27064 cultivation, Salem-Berkhit et al observed that three out of eight tested oils supported CA production [ 99 ] and that the olive oil-containing medium ensured a CA concentration twice as high as glycerol-containing medium.…”

Screening of wild type Streptomyces isolates able to overproduce clavulanic acid

“…Although CA is produced by several species of Streptomyces ( Butterworth, 1984 ), its industrial production is almost entirely dependent on S. clavuligerus cultivation in complex medium ( Silva et al , 2012 ). In view to produce clavulanic acid by S. clavuligerus , several components of industrial culture media such as starch and other carbohydrates are not essential ( Efthimiou et al , 2008 ), therefore alternative carbon sources are evaluated to synthesize this antibiotic. Lee and Ho (1996) obtained the highest productivity employing palm oil as carbon source, but other carbons sources such as maltose and dextrin were successfully employed ( Pruess and Kellett, 1983 ).…”