New Lactimidomycin Congeners Shed Insight into Lactimidomycin Biosynthesis in Streptomyces amphibiosporus

Abstract
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 ∼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.

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