New lactimidomycin congeners shed insight into lactimidomycin biosynthesis in Streptomyces amphibiosporus.
Lactimidomycin (LTM, 1) is a macrolide antitumor antibiotic with a glutarimide side chain from Streptomyces amphibiosporus ATCC53964. To further develop LTM and related analogues as drug candidates we have (i) improved LTM production by approximately 20 fold, (ii) identified three new metabolites (2-4) possibly involved in the LTM biosynthetic pathway; (iii) found 3 to be identical with a previously identified isomigrastatin precursor, (iv) determined the absolute stereochemistry of LTM, and (v) produced new LTM rearrangement products 2a-d and 4a-d.
Ju
Jianhua
J
Division of Pharmaceutical Sciences, University of Wisconsin National Cooperative Drug Discovery Group, and Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin 53705-2222, USA.
Seo
Jeong-Woo
JW
Her
Yeng
Y
Lim
Si-Kyu
SK
Shen
Ben
B
D001688:Biological Products / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D018942:Macrolides / Q000737:chemistry* / Q000378:metabolism*; D015394:Molecular Structure; D010881:Piperidones / Q000737:chemistry* / Q000378:metabolism*; D013302:Streptomyces / Q000737:chemistry* / Q000378:metabolism*
D001688:Biological Products; D018942:Macrolides; D010881:Piperidones; C077633:lactimidomycin; C007864:glutarimide