New Alpiniamides From Streptomyces sp. IB2014/011-12 Assembled by an Unusual Hybrid Non-ribosomal Peptide Synthetase Trans-AT Polyketide Synthase Enzyme

Abstract

The environment of Lake Baikal is a well-known source of microbial diversity. The strain <i>Streptomyces</i> sp. IB2014/011-12, isolated from samples collected at Lake Baikal, was found to exhibit potent activity against Gram-positive bacteria. Here, we report isolation and characterization of linear polyketide alpiniamide A <b>(1)</b> and its new derivatives B-D <b>(2-5)</b>. The structures of alpiniamides A-D were established and their relative configuration was determined by combination of partial Murata's method and ROESY experiment. The absolute configuration of alpiniamide A was established through Mosher's method. The gene cluster, responsible for the biosynthesis of alpiniamides (<i>alp</i>) has been identified by genome mining and gene deletion experiments. The successful expression of the cloned <i>alp</i> gene cluster in a heterologous host supports these findings. Analysis of the architecture of the <i>alp</i> gene cluster and the feeding of labeled precursors elucidated the alpiniamide biosynthetic pathway. The biosynthesis of alpiniamides is an example of a rather simple polyketide assembly line generating unusual chemical diversity through the combination of domain/module skipping and double bond migration events.