full issue - Association of Biotechnology and Pharmacy
full issue - Association of Biotechnology and Pharmacy
full issue - Association of Biotechnology and Pharmacy
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Current Trends in <strong>Biotechnology</strong> <strong>and</strong> <strong>Pharmacy</strong><br />
Vol. 5 (3) 1325 -1337 July 2011, ISSN 0973-8916 (Print), 2230-7303 (Online)<br />
1329<br />
(11). Fig. 1 shows the effect <strong>of</strong> different carbon<br />
sources on cephamycin C production. The<br />
medium was supplemented with<br />
monosaccharide, disaccharide, polysaccharide<br />
<strong>and</strong> oils as carbon source. Only glycerol <strong>and</strong><br />
soybean oil was found to be promising. Glycerol<br />
supported maximum production <strong>of</strong> 324.67 ± 7.13<br />
mg/l, while soybean oil supported 313.26 ± 11.09<br />
mg/l <strong>of</strong> cephamycin C after 88 h <strong>of</strong> fermentation.<br />
Hence, for all further studies, glycerol was used<br />
as a carbon source. Addition <strong>of</strong> fructose, maltose,<br />
galactose <strong>and</strong> coconut oil as carbon source did<br />
not have any major effect on cephamycin C<br />
production. The production <strong>of</strong> cephamycin C<br />
decreased with sucrose, starch <strong>and</strong> lactose to as<br />
low as 201.4 ± 4.03 mg/l as compared to glucose.<br />
This inverse relationship between specific<br />
productivity <strong>and</strong> lactose concentration suggested<br />
the presence <strong>of</strong> some type <strong>of</strong> carbon catabolite<br />
regulation (12). Park et al. (13) reported the<br />
maximum production <strong>of</strong> 525.4 mg/l <strong>of</strong><br />
Fig. 1. Effect <strong>of</strong> carbon source on cephamycin C production<br />
by N. lactamdurans NRRL 3802 in SmF<br />
cephamycin C using Streptomyces sp. p6621<br />
when soybean oil was used alone as carbon<br />
source at 30g/l.<br />
Effect <strong>of</strong> inorganic <strong>and</strong> organic nitrogen<br />
sources: Nitrogen compounds also play an<br />
important role in determining both the growth<br />
<strong>and</strong> product yield in antibiotic fermentations.<br />
Nitrogen must be introduced to the culture in a<br />
manner which satisfy both the growth <strong>and</strong><br />
antibiotic synthesis, but which restricts neither.<br />
Nitrogen sources such as yeast extract, peptone,<br />
malt extract, urea, NH 4<br />
Cl, (NH 4<br />
) 2<br />
HPO 4,<br />
(NH 4<br />
)H 2<br />
PO 4<br />
, NH 4<br />
SO 4<br />
<strong>and</strong> NH 4<br />
NO 3<br />
were added<br />
at 1 g/l to select a suitable nitrogen source for<br />
cephamycin C production (data not shown). Of<br />
the selected inorganic <strong>and</strong> organic nitrogen<br />
sources, yeast extract gave a maximum yield <strong>of</strong><br />
348.03 ± 14.62 mg/l <strong>of</strong> cephamycin C <strong>and</strong><br />
(NH 4<br />
)H 2<br />
PO 4<br />
gave the least (250.10 ± 22.61 mg/<br />
l). Hence, further studies were carried out using<br />
yeast extract as nitrogen source.<br />
Ammonia regulation <strong>of</strong> antibiotic synthesis<br />
has been reported for several other secondary<br />
metabolite producing organisms (14).<br />
Aharonowitz <strong>and</strong> Demain (15) have observed a<br />
strong suppressive effect <strong>of</strong> ammonia on<br />
antibiotic production in the cephamycin producer<br />
Streptomyces clavuligerus. Brana et al. (16) have<br />
also reported effect <strong>of</strong> ammonium on<br />
cephamycin C production. When increasing<br />
concentration <strong>of</strong> NH 4<br />
Cl were added to the<br />
st<strong>and</strong>ard medium containing 15 mM asparagines,<br />
there was a progressive <strong>and</strong> strong decrease in<br />
the production <strong>of</strong> cephalosporins. Ammonium<br />
chloride depressed cephalosporin production (by<br />
about 75%), presumably as a result <strong>of</strong> repression<br />
<strong>of</strong> cyclase <strong>and</strong> exp<strong>and</strong>ase formation, but not <strong>of</strong><br />
epimerase. Khaoua et al. (17) studied the effect<br />
<strong>of</strong> nitrogen source on production <strong>of</strong> cephamycin<br />
C by S. cattleya <strong>and</strong> found the production to vary<br />
with the use <strong>of</strong> asparagines, glutamine or<br />
ammonium as nitrogen sources.<br />
This hypothesis is supported by studies<br />
done with cephamycin producing organism, N.<br />
lactamdurans. Ginther (7) observed that<br />
conditions which led to such secondary processes<br />
Sequential optimization <strong>of</strong> cephamycin C