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 />
1331<br />
Cephamycin C (mg/l) DCW (g/l)<br />
Fig. 3. Effect <strong>of</strong> minerals on cephamycin C production by N. lactamdurans NRRL 3802 by SmF<br />
have inhibitory effect on the production <strong>of</strong><br />
cephamycin C. Whereas, removal <strong>of</strong> NaCl,<br />
MgSO 4<br />
, FeSO 4<br />
, Na 2<br />
S 2<br />
O 3<br />
<strong>and</strong> K 2<br />
HPO 4<br />
decreased<br />
the production <strong>of</strong> cephamycin C suggesting them<br />
to play an important role in the production <strong>of</strong><br />
cephamycin C.<br />
Calcium has been identified to be inhibitory<br />
to the biosynthesis <strong>of</strong> cephamycin C in resting<br />
cells <strong>of</strong> N. lactamdurans (21). Therefore, calcium<br />
probably does not directly interfere with the<br />
biosynthetic enzymes for either cephamycin C<br />
or efrotomycin. Inhibition is more likely to be<br />
caused by calcium interfering with an enzyme<br />
or cellular process, which is generally the case<br />
in secondary metabolism (22). MgSO 4<br />
is a<br />
c<strong>of</strong>actor for the enzyme ACV synthetase, <strong>and</strong><br />
FeSO 4<br />
for isopenicillin N synthase (IPN<br />
synthase) <strong>and</strong> deacetoxycephalosporin C<br />
synthase (DAOC synthase). Hence they are<br />
essentially required by these enzymes for the<br />
biosynthesis <strong>of</strong> cephamycin C. Sulphur from<br />
sodium thiosulphate gets incorporated into<br />
cysteine by reduction, <strong>and</strong> ultimately into â-<br />
lactam products. Phosphate, despite not being<br />
incorporated directly into the â-lactam nucleus,<br />
affects secondary metabolism in â-lactam<br />
producing organisms. They can independently<br />
inhibit enzyme action, regulate protein<br />
expression <strong>and</strong> limit cell growth.<br />
Optimization <strong>of</strong> fermentation medium using<br />
statistical methods<br />
Optimization using the L 16<br />
-orthogonal array:<br />
Taguchi design was used to determine most<br />
significant factors which affect the production<br />
<strong>of</strong> cephamycin C. The 8 factors selected were<br />
glycerol, yeast extract, L-glutamic acid, K 2<br />
HPO 4<br />
,<br />
NaCl, MgSO 4<br />
, FeSO 4<br />
<strong>and</strong> Na 2<br />
S 2<br />
O 3<br />
. The<br />
concentrations <strong>of</strong> the medium components were<br />
selected based on the production medium<br />
composition that was optimized using one factor<br />
at a time.<br />
Table 4 represents the response table for<br />
means (larger is better) <strong>and</strong> for signal to noise<br />
ratio obtained with L 16<br />
-orthogonal array. The last<br />
two columns in the Table 4 document the delta<br />
Sequential optimization <strong>of</strong> cephamycin C