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Pathway Description
Avermectin A1a biosynthesis
Streptomyces avermitilis
Metabolic Pathway
Avermectin A1a biosynthesis involves multiple enzymatic steps that convert simple precursors like 2-methylbutyryl-CoA, malonyl-CoA, and methylmalonyl-CoA into the final potent anthelmintic compound. The process begins with chain elongation by type I polyketide synthase (PKS) AVES 1, forming 6,8a-seco-6,8a-deoxy-5-oxoavermectin "1a" aglycone. This intermediate is hydroxylated by cytochrome P450 hydroxylase, reduced by C-5 ketoreductase to avermectin B1a aglycone, and methylated by C5-O-methyltransferase to form avermectin A1a aglycone. Finally, glycosyltransferases add sugar moieties, resulting in avermectin A1a. This biosynthetic pathway yields aAvermectin A1a which has significant agricultural and medical applications as well as protecting bacteria from other competitive microorganisms.
References
Avermectin A1a biosynthesis References
Kanehisa, M., 2002, November. The KEGG database. In ‘In silico’simulation of biological processes: Novartis Foundation Symposium 247 (Vol. 247, pp. 91-103). Chichester, UK: John Wiley & Sons, Ltd.
Liu W, Zhang Q, Guo J, Chen Z, Li J, Wen Y: Increasing Avermectin Production in Streptomyces avermitilis by Manipulating the Expression of a Novel TetR-Family Regulator and Its Target Gene Product. Appl Environ Microbiol. 2015 Aug;81(15):5157-73. doi: 10.1128/AEM.00868-15. Epub 2015 May 22.
Pubmed: 26002902
UniProt Consortium, 2019. UniProt: a worldwide hub of protein knowledge. Nucleic acids research, 47(D1), pp.D506-D515.
Kim, S., Thiessen, P.A., Bolton, E.E., Chen, J., Fu, G., Gindulyte, A., Han, L., He, J., He, S., Shoemaker, B.A. and Wang, J., 2016. PubChem substance and compound databases. Nucleic acids research, 44(D1), pp.D1202-D1213.
de Matos, P., Adams, N., Hastings, J., Moreno, P. and Steinbeck, C., 2012. A database for chemical proteomics: ChEBI. Chemical Proteomics: Methods and Protocols, pp.273-296.
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