{PDOC00165}
{PS00185; IPNS_1}
{PS00186; IPNS_2}
{BEGIN}
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* Isopenicillin N synthase signatures *
***************************************

Isopenicillin N  synthase  (EC  1.21.3.1)  (IPNS) [1,2] is a key enzyme in the
biosynthesis of  penicillin  and cephalosporin.  In the presence of oxygen, it
removes  iron and ascorbate, four hydrogen atoms from L-(alpha-aminoadipyl)-L-
cysteinyl-d-valine to   form   the   azetidinone  and  thiazolidine  rings  of
isopenicillin.  IPNS is  an  enzyme  of  about  330  amino-acid  residues. Two
cysteines are  conserved in fungal and bacterial  IPNS  sequences;  these  may
be involved in iron-binding and/or substrate-binding.

Cephalosporium acremonium DAOCS/DACS [3] is a bifunctional  enzyme involved in
cephalosporin biosynthesis. The DAOCS domain, which is structurally related to
IPNS, catalyzes the step from penicillin N to deacetoxy-cephalosporin C - used
as a   substrate   by  DACS  to  form  deacetylcephalosporin  C.  Streptomyces
clavuligerus possesses  a  monofunctional  DAOCS  enzyme  (gene cefE) [4] also
related to IPNS.

We derived  two  signature  patterns  for  these  enzymes, centered around the
conserved cysteine residues.

-Consensus pattern: [RK]-x-[STA]-x(2)-S-x-C-Y-[SL]
                    [C may be an active site residue]
-Sequences known to belong to this class detected by the pattern: ALL,  except
 for Streptomyces clavuligerus  DAOCS  which has  Ser in the first position of
 the pattern.
-Other sequence(s) detected in Swiss-Prot: 6.

-Consensus pattern: [LIVM](2)-x-C-G-[STA]-x(2)-[STAG]-x(2)-T-x-[DNG]
                    [C may be an active site residue]
-Sequences known to belong to this class detected by the pattern: ALL,  except
 for Nocardia lactamdurans IPNS.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Last update: May 2004 / Text revised.

[ 1] Martin J.F.
     Trends Biotechnol. 5:306-308(1987).
[ 2] Chen G., Shiffman D., Mevarech M., Aharonowitz Y.
     Trends Biotechnol. 8:105-111(1990).
[ 3] Samson S.M., Dotzlaf J.E., Slisz M.L., Becker G.W., van Frank R.M.,
     Veal L.E., Yeh W.K., Miller J.R., Queener S.W., Ingolia T.D.
     Bio/Technology 5:1207-1214(1987).
[ 4] Kovacevic S., Weigel B.J., Tobin M.B., Ingolia T.D., Miller J.R.
     "Cloning, characterization, and expression in Escherichia coli of the
     Streptomyces clavuligerus gene encoding deacetoxycephalosporin C
     synthetase."
     J. Bacteriol. 171:754-760(1989).
     PubMed=2644235

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{END}