Expanding the Structural Diversity of Drimentines by Exploring the Promiscuity of Two N-methyltransferases.
作者： Tingting Yao , Jing Liu , Enjing Jin , Zengzhi Liu , Huayue Li
DOI: 10.1016/J.ISCI.2020.101323
关键词:
摘要: Methylation is envisioned as a promising way to rationally improve key pharmacokinetic characteristics of lead compounds. Although diverse tailoring enzymes are found be clustered with cyclodipeptide synthases (CDPSs) perform further modification reactions on the diketopiperazine (DKP) rings generating complex DKP-containing compounds, so far, limited number methyltransferases (MTs) co-occurring CDPS have been experimentally characterized. Herein, we deciphered methylation steps during drimentines (DMTs) biosynthesis identification and characterization DmtMT2-1 (from Streptomyces sp. NRRL F-5123) DmtMT1 youssoufiensis OUC6819). catalyzes N4-methylation both pre-DMTs DMTs; conversely, recognizes DKP rings, functioning before assembly terpene moiety. Notably, MTs display broad substrate promiscuity. Their combinatorial expression dmt1 genes in different strains successfully generated eight unnatural DMT analogs. Our results enriched MT tool-box, setting stage for exploring structural diversity derivatives drug development.
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