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- *****************************************
- * Isopenicillin N synthetase signatures *
- *****************************************
-
- 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).
-