A second type-I PKS gene cluster isolated from Streptomyces hygroscopicus ATCC 29253, a rapamycin-producing strain

Gene. 1997 Dec 5;203(1):1-9. doi: 10.1016/s0378-1119(97)00450-2.


Analysis of a 32.8-kb segment of DNA from the rapamycin (Rp) producer, Streptomyces hygroscopicus ATCC 29253, revealed a new type-I polyketide synthase (PKS) cluster consisting of four open reading frames (ORF 1-4), each encoding a single PKS module. The four ORFs are transcribed in the same direction and are flanked by several smaller ORFs (ORF 5-9), which may be related to the PKS cluster. The first PKS-containing ORF has a ligase domain at the N-terminus of the polypeptide. This domain has 55% aa identity to the CoA ligase domain of the Rp PKS (Schwecke et al., 1995. Proc. Natl. Acad. Sci. 92, 7839-7843) which is also encoded in this strain (Lowden et al., 1996. Angew. Chem. Int. Ed. Engl. 35, 2249-2251). ORF5 (340 aa) and ORF6 (924 aa) were found to be homologous to RapK (41% aa identity) and RapH (35% aa identity), which are hypothesized to be a pteridine-dependent dioxygenase and a regulatory protein, respectively (Molnar et al., 1996. Gene 169, 1-7). In addition, ORF7 (391 aa) was found to have up to 42% aa identity to a number of plant 3-deoxy-D-arabino-heptulosonate-7-phosphate synthases (DAHPS) and 47% aa identity to PhzF, a bacterial DAHPS involved in phenazine antibiotic synthesis. The proximity of the DAHPS-encoding gene to the PKS cluster containing a Rp-like ligase domain suggests that a derivative of shikimate may be used as the PKS starter. ORF8 (283 aa) was found to have homology (32% aa identity) to a Synechocystis sp. gene of unknown function. The N-terminal portion of ORF9 was found to be similar to a tetracycline 6-hydroxylase (34% aa identity) from Streptomyces aureofaciens.

MeSH terms

  • 3-Oxoacyl-(Acyl-Carrier-Protein) Synthase / genetics
  • Acyl Carrier Protein / genetics
  • Acyltransferases / genetics
  • Alcohol Oxidoreductases / genetics
  • Amino Acid Sequence
  • Bacterial Proteins*
  • Base Sequence
  • DNA, Bacterial
  • Enoyl-(Acyl-Carrier-Protein) Reductase (NADH)
  • Hydro-Lyases / genetics
  • Isoenzymes / genetics
  • Ligases
  • Molecular Sequence Data
  • Multienzyme Complexes / genetics*
  • Multigene Family*
  • Open Reading Frames
  • Oxidoreductases / genetics
  • Polyenes / metabolism*
  • Sirolimus
  • Streptomyces / enzymology*
  • Streptomyces / genetics


  • Acyl Carrier Protein
  • Bacterial Proteins
  • DNA, Bacterial
  • Isoenzymes
  • Multienzyme Complexes
  • Polyenes
  • Oxidoreductases
  • Alcohol Oxidoreductases
  • polyketide synthase ketoreductase
  • Enoyl-(Acyl-Carrier-Protein) Reductase (NADH)
  • Acyltransferases
  • beta-ketoacyl-acyl carrier protein synthase I
  • 3-Oxoacyl-(Acyl-Carrier-Protein) Synthase
  • Hydro-Lyases
  • Ligases
  • Sirolimus

Associated data

  • GENBANK/AF007101