Organization of biosynthetic gene cluster for avermectin in Streptomyces avermitilis: analysis of enzymatic domains in four polyketide synthases

Citation
H. Ikeda et al., Organization of biosynthetic gene cluster for avermectin in Streptomyces avermitilis: analysis of enzymatic domains in four polyketide synthases, J IND MIC B, 27(3), 2001, pp. 170-176
Citations number
26
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biotecnology & Applied Microbiology",Microbiology
Journal title
JOURNAL OF INDUSTRIAL MICROBIOLOGY & BIOTECHNOLOGY
ISSN journal
1367-5435 → ACNP
Volume
27
Issue
3
Year of publication
2001
Pages
170 - 176
Database
ISI
SICI code
1367-5435(200109)27:3<170:OOBGCF>2.0.ZU;2-9
Abstract
The analysis of the incorporation of C-13-labeled precursors into avermecti ns indicates that the avermectin aglycons are synthesized by head-to-tail c ondensation of various acyl groups, which is similar to the biosynthesis of other polyketides. Polyketide synthases (PKS) use the appropriate CoA este r as a primer and add acetate units from malonyl-CoA and propionate units f rom methylmalonyl-CoA to assemble the polyketides. Avermectin aglycons are formed by addition to the starter unit (2-methylbutyrate or isobutyrate) of 12 acyl condensations in the order P-A-A-A-A-P-P-A-P-A-P-A (P, propionyl; A, acetyl). Within the 90-kb gene cluster for avermectin biosynthesis, the central 65-kb segment was found to be required for aglycon biosynthesis by phenotypic analysis of strains containing deletion or insertion mutations i n this region. A complete sequence analysis of the 65-kb segment indicated that this segment encodes avermectin PKS. The avermectin PKS genes are orga nized into two converging blocks of ORFs. From the results of sequencing an alysis, a feature of the two regions, aveA1/aveA2 and ave3/aveA4, is that t hey encode four kinds of large multifunctional polypeptides containing 55 d omains which possess putative fatty acid synthase-like activities. The aver mectin PKS (AVES 1-4) appear to contain two, three, or four modules. AVES 1 and 2 contain two and four modules, respectively, whereas AVES 3 and AVES 4 each contains three modules. The 12 modules correspond to the 12 cycles r equired for synthesis of the avermectin aglycon.