| Literature DB >> 30855966 |
Lei Dong1,2, Yi Shen3, Xian-Feng Hou3, Wen-Jun Li1,2, Gong-Li Tang3.
Abstract
The biosynthetic gene cluster of antitumor antibiotic LL-D49194α1 (LLD) was identified and comparatively analyzed with that of trioxacarcins. The tailoring genes encoding glycosyltransferase, methyltransferase and cytochrome P450 were systematically deleted, which led to the discovery of eight compounds from the mutants. Preliminary pharmaceutical evaluation revealed two intermediates exhibiting higher cytotoxicity, stability and solubility. These results highlighted the modification pathway for LLD biosynthesis, and provided highly potent, structurally simplified "unnatural" natural products with improved druggability.Entities:
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Year: 2019 PMID： 30855966 DOI： 10.1021/acs.orglett.9b00610
Source DB: PubMed Journal: Org Lett ISSN： 1523-7052 Impact factor: 6.005