full issue - Association of Biotechnology and Pharmacy

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