Use of soybean oil and ammonium sulfate additions to optimize secondary metabolite production

Abstract

A valine‐overproducing mutant (MA7040, Streptomyces hygroscopicus) was found to produce 1.5 to 2.0 g/L of the immunoregulant, L‐683,590, at the 0.6 m3 fermentation scale in a simple batch process using soybean oil and ammonium sulfate‐based GYG5 medium. Levels of both lower (L‐683,795) and higher (HH1 and HH2) undesirable homolog levels were controlled adequately. This batch process was utilized to produce broth economically at the 19 m3 fermentation scale. Material of acceptable purity was obtained without the multiple pure crystallizations previously required for an earlier culture, MA6678, requiring valine supplementation for impurity control. Investigations at the 0.6 m3 fermentation scale were conducted, varying agitation, pH, initial soybean oil/ammonium sulfate charges, and initial aeration rate to further improve growth and productivity. Mid‐cycle ammonia levels and lipase activity appeared to have an important role. Using mid‐cycle soybean oil additions, a titer of 2.3 g/L of L‐683,590 was obtained, while titers reached 2.7 g/L using mid‐cycle soybean oil and ammonium sulfate additions. Both higher and lower homolog levels remained acceptable during this fed‐batch process. Optimal timing of mid‐cycle oil and ammonium sulfate additions was considered a critical factor to further titer improvements. © 1998 John Wiley & Sons, Inc. Biotechnol Bioeng 60: 580–588, 1998.

Aeration of Liquid‐Liquid Systems Using Various Agitators in a Mixer Equipped with a Membrane Diffuser

“…Gas sparging onto an impeller agitating liquids and thus achieving effective contact between the sparged gas and the liquid phase is a vital feature in several chemical and biochemical processes. Gas‐liquid (G‐L) or gas‐liquid‐liquid (G‐L‐L) agitations are used in physical and chemical gas absorption 1, 2, aerobic fermentation 3, 4, catalytic hydrogenation of vegetable oils 5, 6, oxidation of hydrocarbons 7, 8, hydroformylation and carbonylation 9, as well as in the food industry 10 and in wastewater treatment 11–13. In general, investigations of G‐L‐L dispersions in stirred tanks were focused on the minimum agitation speed for reaching complete liquid–liquid (L‐L) dispersion 14, 15, the effect of a second liquid on the G‐L interfacial surface 16–19, the mixing time 20, the gas absorption rate 21–23, catalytic aspects 24, and mass transfer 25–27.…”

Actinomycetes scale‐up for the production of the antibacterial, nocathiacin

“…Other relevant examples of foam formation during sterilization and early cultivation were evident in the literature: Sterilized 15 g/L and 30 g/L hydrolyzed casein solutions required three‐fold longer to form foam 24 h after sterilization compared with directly after sterilization, which was believed due to “aging” of broth proteins, and “aged” broth also was found to prolong the effect of antifoam additions (Szarka and Magyar,1969). For the production of immunomycin by S. hygroscopicus , foaming was reproducibly observed 12–18 h postinoculation at the 15,000 L scale for 6–10 h, and it was more severe in fermentors with hydrofoil rather than Rushton impellers (Junker et al,1998b). When foam was controlled using antifoam, there was no effect on titer; when foam was controlled by reducing aeration from 0.3 to 0.075 vvm and increasing backpressure (up to 0.18 MPa), initial production rates were reduced by 33% (Junker et al,1998b).…”

“…For the production of immunomycin by S. hygroscopicus , foaming was reproducibly observed 12–18 h postinoculation at the 15,000 L scale for 6–10 h, and it was more severe in fermentors with hydrofoil rather than Rushton impellers (Junker et al,1998b). When foam was controlled using antifoam, there was no effect on titer; when foam was controlled by reducing aeration from 0.3 to 0.075 vvm and increasing backpressure (up to 0.18 MPa), initial production rates were reduced by 33% (Junker et al,1998b).…”

Nutritional requirements for the production of dithiolopyrrolone antibiotics by Saccharothrix algeriensis NRRL B-24137

“…The selection of appropriate carbon and nitrogen sources can have a great effect on the production levels of secondary metabolites [15]. Nutrients such as amino acids can often act as both carbon and nitrogen sources.…”