Nucleotide sequence and deduced functions of a set of cotranscribed genes of Streptomyces coelicolor A3(2) including the polyketide synthase for the antibiotic actinorhodin

• Published in: The Journal of biological chemistry 1992-09, Vol.267 (27), p.19278-19290
• Main Authors: FERNANDEZ-MORENO, M. A, MARTINEZ, E, BOTO, L, HOPWOOD, D. A, MALPARTIDA, F
• Format: Article
• Language: English
• Subjects: actinorhodin; Acyl Carrier Protein - genetics; Acyltransferases - genetics; Amino Acid Sequence; Anthraquinones - metabolism; Bacterial Proteins - genetics; Base Sequence; Biological and medical sciences; biosynthesis; Cloning, Molecular; DNA, Bacterial - genetics; enzymes; Fundamental and applied biological sciences. Psychology; genes; Genes, Bacterial; Genes. Genome; Genetic Complementation Test; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; Multienzyme Complexes - genetics; nucleotide sequence; Operon; polyketide synthase; prediction; Restriction Mapping; Sequence Alignment; Streptomyces - genetics; Streptomyces coelicolor
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/s0021-9258(18)41772-3

A 5.3-kb region of the Streptomyces coelicolor actinorhodin gene cluster, including the genes for polyketide biosynthesis, was sequenced. Six identified open reading frames (ORF1-6) were related to genetically characterized mutations of classes actI, VII, IV, and VB by complementation analysis. ORF1-6 run divergently from the adjacent actIII gene, which encodes the polyketide synthase (PKS) ketoreductase, and appear to form an operon. The deduced gene products of ORF1-3 are similar to fatty acid synthases (FAS) of different organisms and PKS genes from other polyketide producers. The predicted ORF5 gene product is similar to type II beta-lactamases of Bacillus cereus and Bacteroides fragilis. The ORF6 product does not resemble other known proteins. Combining the genetical, biochemical, and similarity data, the potential activities of the products of the six genes can be postulated as: 1) condensing enzyme/acyl transferase (ORF1 + ORF2); 2) acyl carrier protein (ORF3); 3) putative cyclase/dehydrase (ORF4); 4) dehydrase (ORF5); and 5) "dimerase" (ORF6). The data show that the actinorhodin PKS consists of discrete monofunctional components, like that of the Escherichia coli (Type II) FAS, rather than the multifunctional polypeptides for the macrolide PKSs and vertebrate FASs (Type I).