Pyrrolopyrimidines are an important class of natural products with a broad spectrum of biological activities, including antibacterial, antifungal, antiviral, anticancer or anti-inflammatory. Here, we present the identification of a biosynthetic gene cluster from the rare actinomycete strain Kutzneria albida DSM 43870, which leads to the production of huimycin, a new member of the pyrrolopyrimidine family of compounds. The huimycin gene cluster was successfully expressed in the heterologous host strain Streptomyces albus Del14. The compound was purified, and its structure was elucidated by means of nuclear magnetic resonance spectroscopy. The minimal huimycin gene cluster was identified through sequence analysis and a series of gene deletion experiments. A model for huimycin biosynthesis is also proposed in this paper.

Isoquinoline alkaloids are a large class of natural products with a broad range of biological activities, including antimicrobial, antitumor, antileukemic and anti-inflammatory properties. Although mostly found in plants, isoquinolines can also be found in the extracts of bacterial and fungal cultures. Regardless of the origin, most of the reported biosynthetic routes for isoquinolines use tyrosine as a main biosynthetic precursor. Here, we report the identification of a new biosynthetic pathway for production of isoquinolinequinone alkaloid mansouramycin D in Streptomyces albus Del14. Using feeding, mass spectrometry, and nuclear magnetic resonance spectroscopy, we demonstrate that tryptophan serves instead of tyrosine as a main mansouramycin biosynthetic precursor. The biosynthetic genes were identified in the chromosome of the strain by using gene inactivation and heterologous expression. Insights into the biosynthesis of mansouramycins are also presented.

No abstract