Characterisation of a Streptomyces antibioticus gene encoding a type I polyketide synthase which has an unusual coding sequence

Abstract

A gene (ORFB) from Streptomyces antibioticus (an oleandomycin producer) encoding a large, multifunctional polyketide synthase (PKS) was cloned and sequenced. Its product shows an internal duplication and a close similarity to the third subunit of the PKS involved in erythromycin biosynthesis by Saccharopolyspora erythraea, showing the equivalent nine active site domains in the same order along the polypeptide. An unusual feature of this ORF is the GC content of most of the sequence, which is surprisingly low, for a Streptomyces gene; the large number of codons with T in the third position is particularly striking. The last 800 bp of the gene stand out as being normal in their GC content, this region corresponding almost exactly to the thioesterase domain of the gene and suggesting that this domain was a late addition to the PKS. Based on the high degree of similarity between the ORFB product and the third subunit of the erythromycin PKS and the occurrence nearby of a gene conferring oleandomycin resistance, it is possible that this gene might be involved in the biosynthesis of the oleandomycin lactone ring.

Divergent sequence motifs correlated with the substrate specificity of (methyl)malonyl‐CoA:acyl carrier protein transacylase domains in modular polyketide synthases

“…It may be seen in Fig. 1 that the two AT domain sequences published for the polyketide synthase for the macrolide oleandomycin (which contains propionate extender units only) [13] both match the propionate motif exactly. Sequence data have also been obtained (Galloway, I.S.…”

“…Rap 1-14 indicate the different AT domains present in modules 1-14 of the PKS for rapamycin biosynthesis [7]. Ery 1 6, Ave 2, Ole 5 and 6, Nem 6 and 9, and Sor 5, indicate AT domains present in the corresponding modules of the modular PKSs for erythromycin [3,4], avermectin, oleandomycin [13], nemadectin [14] and soraphen A [15] biosynthesis respectively. MSAS represents the 6-methylsalicylic acid synthase AT [16], and MAS that of mycocerosic acid synthase [17].…”

Functional Analysis of OleY l -Oleandrosyl 3- O -Methyltransferase of the Oleandomycin Biosynthetic Pathway in Streptomyces antibioticus

“…Structurally it contains a macrolactone ring (oleandolide) which is synthesized by the assembly of one starter acetylcoenzyme A (CoA) and six extender methylmalonyl CoA units. These reactions are catalyzed by a modular type I polyketide synthase comprising three large polypeptides, named OleA1, OleA2, and OleA3 (24,25). The oleandomycin biosynthetic gene cluster has been fully sequenced and characterized (1,15,16,18,19,24,25) (Fig.…”

A polyketide biosynthetic gene cluster from Streptomyces antibioticus includes a LysR-type transcriptional regulator

“…A gene cluster was isolated from S. antibioticus, a strain known to produce the macrolide antibiotic oleandomycin and to contain the Type I PKS genes (Swan et al, 1994). As in many other actinomycetes, S. antibioticus 11891 contains several actI-hybridizing fragments (Malpartida et al, 1987) ; the possibility that some of them are involved in the biosynthesis of well known, spore-associated pigments (Davis & Chater, 1990 ;Blanco et al, 1992Blanco et al, , 1993) cannot be ruled out.…”