Lentzeacins A-E, New Bacterial-Derived 2,5- and 2,6-Disubstituted Pyrazines from a BGC-Rich Soil Bacterium <i>Lentzea</i> sp. GA3-008

Pyrazines (1,4-diazirines) are an important group of natural products that have tremendous monetary value in the food and fragrance industries and can exhibit a wide range of biological effects including antineoplastic, antidiabetic and antibiotic activities. As part of a project investigating the s...

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Bibliographic Details
Main Authors: Hong-Bing Liu, Jack R. Davison, Rahim Rajwani, Gengxiang Zhao, Shannon I. Ohlemacher, Robert D. O’Connor, Carole A. Bewley
Format: Article
Language:English
Published: MDPI AG 2021-11-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/26/23/7197
Description
Summary:Pyrazines (1,4-diazirines) are an important group of natural products that have tremendous monetary value in the food and fragrance industries and can exhibit a wide range of biological effects including antineoplastic, antidiabetic and antibiotic activities. As part of a project investigating the secondary metabolites present in understudied and chemically rich Actinomycetes, we isolated a series of six pyrazines from a soil-derived <i>Lentzea</i> sp. GA3-008, four of which are new. Here we describe the structures of lentzeacins A-E (<b>1</b>, <b>3</b>, <b>5</b> and <b>6</b>) along with two known analogues (<b>2</b> and <b>4</b>) and the porphyrin zincphyrin. The structures were determined by NMR spectroscopy and HR-ESI-MS. The suite of compounds present in <i>Lentzea</i> sp. includes 2,5-disubstituted pyrazines (compounds <b>2</b>, <b>4</b>, and <b>6</b>) together with the new 2,6-disubstituted isomers (compounds <b>1</b>, <b>3</b> and <b>5</b>), a chemical class that is uncommon. We used long-read Nanopore sequencing to assemble a draft genome sequence of <i>Lentzea</i> sp. which revealed the presence of 40 biosynthetic gene clusters. Analysis of classical di-modular and single module non-ribosomal peptide synthase genes, and cyclic dipeptide synthases narrows down the possibilities for the biosynthesis of the pyrazines present in this strain.
ISSN:1420-3049