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* Isopenicillin N synthetase signatures *
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Isopenicillin N synthetase (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]
-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: a 24 Kd mycobacterial  hypothetical
 protein.

-Consensus pattern: [LIVM](2)-x-C-G-[STA]-x(2)-[STAG]-x(2)-T-x-[DNG]
-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: December 1992 / 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.
     J. Bacteriol. 171:754-760(1989).