Streptomyces avermitilis

Denoya CD, DD Skinner, MR Morgenstern (1994) A Streptomyces avermitilis gene encoding a 4-hydroxy-phenylpyruvic acid dioxygenase-like protein that directs the production of homogentisic acid and an ochronotic pigment in Escherichia coli. J Bacterial 176 5312-5319. 

Johnson-Winters K, VM Purpero, M Kavana, T Nelson, GR Moran (2003) (4-Hydroxyphenyl)pyruvate dioxygenase from Streptomyces avermitilis the basis for ordered substrate addition. Biochemistry 42 2072-2080. 

Stutzman-Engwall, K., Conlon, S., Fedechko, R. et al. (2003) Engineering the aveC gene to enhance the ratio of doramectin to its CHC-B2 analogue produced in Streptomyces avermitilis. Biotechnology and Bioengineering, 82, 359-369. 

Ikeda, H., Nonomiya, T., Usami, M. et aL (1999) Organization of the biosynthetic gene cluster for the polyketide anthelmintic macrolide avermectin in Streptomyces avermitilis. Proceedings of the National Academy of Sciences of the United States of America, 96, 9509-9514. 

Hafner, E.W., Holley, B.W., Holdom, K.S. et al. (1991) Branched-chain fatty acid requirement for avermectin production by a mutant of Streptomyces avermitilis lacking branched-chain 2-oxo acid dehydrogenase activity. Journal of Antibiotics (Tokyo), 44, 349-356. 

Stutzman-Engwall, K.J., Conlon, S.W., Fedechko, R.W. and Kaczmarek, F.S. (1997) Engineering Streptomyces avermitilis biosynthetic genes, in Developments in Industrial Microbiology, vol. 35 (eds. C.R. Hutchinson and J. McAlpine), Society for Industrial Microbiology, Fairfax, VA, pp. 7-13. 

Ikeda, H. and Omura, S. (1995) Control of avermectin biosynthesis in Streptomyces avermitilis for the selective production of a useful component. Journal of Antibiotics (Tokyo), 48, 549-562. 

Stutzman-Engwall K, Conlon S, Fedechko R, McArthur H, Pekrun K, Chen Y, Jenne S, La C, Trinh N, Kim S, Zhang Y-X, Fox R, Gustafsson C, Krebber A. (2005) Semi-synthetic DNA shuffling of aveC leads to improved industrial scale production of doramectin by Streptomyces avermitilis. Metabol Eng 7 21-31. 

The microorganism was classified as a new species of actinomycete. Streptomyces avermitilis. Its anthelmintic activity was shown to reside in 8 closely related macrocyclic lactones, named avermectins, which were also found to possess activity against free-living and parasitic arthropods. One of the natural components, avermectin is now being evaluated as a pesticide for the control of mites of citrus and cotton crops and control of the Red Imported Fire Ant. A chemical derivative, 22,23-dihydroavermectin or ivermectin, has been developed as an antiparasitic agent. It is being marketed for use in cattle, horses and sheep and is expected to become available for swine and dogs. 

The culture, now bearing the product number C-076 and the Merck culture collection number MA-4680, was submitted for taxonomic studies. Its characteristics, including a brownish-gray spore mass color, smooth spore surface, spiral sporophores born as side branches on the aerial mycelia and the production of melanoid pigments, were unlike those of any previously described species of Streptomyces. The culture was named Streptomyces avermitilis, the Streptomyces "capable of separating from worms". 

Semisynthetic derivative of drug obtained from Streptomyces avermitilis. 

Ivermectin, a semisynthetic macrocyclic lactone, is a mixture of avermectin Bia and Bib- is derived from the soil actinomycete Streptomyces avermitilis. 

DD Skinner, MR Morgenstern, RW Fedechko, CD Denoya. Cloning and sequencing of a cluster of genes encoding branched chain a-keto acid dehydrogenase from Streptomyces avermitilis and production of a functional El a[f component in Escherichia coli. J Bacteriol 177 183-190, 1995. 

CD Denoya, RW Fedechko, EW Hafner, HAI McArthur, MR Morgenstern, DD Skinner, K Stutzman-Engwall, RG Wax, WC Wemau. A second branched-chain OC-keto acid dehydrogenase gene cluster (bkdFGH) from Streptomyces avermitilis. its relationship to avermectin biosynthesis and the construction of a bkdF mutant suitable for the production of novel antiparasitic avermectins. J Bacteriol 177 3504-3511, 1995. 

Engineering Streptomyces avermitilis for the Production of Novel Avermectins Mutant Design and Titer Improvement... 

Eight naturally occurring, structurally related avermectins are produced by Streptomyces avermitilis [7], The avermectin polyketide structure is derived from seven acetate and five propionate residues, together with a single 2-methylbutyric acid or isobutyric acid residue which forms the sec-butyl or isopropyl group attached to the C25 of the spiroketal moiety [8,9] (Fig. 1). The avermectin agly-cone is further modified by glycosylation at C13, with the attachment of two O-methylated oleandrose residues and O-methylation at C5. Thus, S. avermitilis... 

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