Rare Polyene-polyol Macrolides from Mangrove-derived Streptomyces sp. ZQ4BG

Wenling Wang,Zhizhen Zhang,Tengfei Song,Lu Chen,Weiyun Chai,Lei Chen,Xiao-Yuan Lian

doi:10.1038/s41598-017-01912-z

Wenling Wang, Zhizhen Zhang + Show 5 more

Open Access

https://doi.org/10.1038/s41598-017-01912-z

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Journal: Scientific Reports	Publication Date: May 10, 2017
Citations: 26	License type: open-access

Affiliation: Zhejiang Ocean University, Zhejiang University

Abstract

Bioactive natural products from mangrove-derived actinomycetes are important sources for discovery of drug lead compounds. In this study, an extract prepared from culture of an actinomycete Streptomyces sp. ZQ4BG isolated from mangrove soils was found to have activity in inhibiting proliferation of glioma cells. Large culture of this mangrove actinomycete in Gause’s liquid medium resulted in isolation of seven novel polyene-polyol macrolides, named as flavofungins III–IX (3–9), together with known flavofungins I (1) and II (2) and spectinabilin (10). Structures of these isolated compounds were elucidated by extensive NMR analyses and HRESIMS data. The stereochemical assignments were achieved by a combination of NOE information, universal NMR database, and chemical reactions including preparation of acetonide derivatives and Mosher esters. Flavofungins IV–VIII (4–8) are rare 32-membered polyene-polyol macrolides with a tetrahydrofuran ring, while flavofungin IX (9) represents the first example of this type of macrolide with a unique oxepane ring. Flavofungins I (1) and II (2) and spectinabilin (10) showed anti-glioma and antifungal activities.

Highlights

Gliomas remain the most common and high death malignant brain tumors despite advances in therapies including chemotherapy, radiotherapy, and surgical resection1–3
An extract prepared from the culture of strain ZQ4BG was found to be the most active against the proliferation of glioma cells with an inhibition of 56.9% for U87MG and 48.9% for U251
ZQ4BG based on its 16S rDNA sequence (Supplementary Information, Fig. S1), which completely (99% identity for a 1404 bp stretch of sequence) matched those of two species of Streptomyces including S. fulvissimus and S. flavofungini (Table S1) in GenBank database

Summary

Introduction

Gliomas remain the most common and high death malignant brain tumors despite advances in therapies including chemotherapy, radiotherapy, and surgical resection1–3. Large culture of this isolated mangrove-derived strain ZQ4BG in Gause’s liquid medium resulted in isolation and identification of a series of polyene-polyol macrolides, including new flavofungins III–IX [3,4,5,6,7,8,9] and known flavofungins I [1] and II [2] and spectinabilin [10].

Results

Conclusion