Discovery of Three 22-Membered Macrolides by Deciphering the Streamlined Genome of Mangrove-Derived Streptomyces sp. HM190.

Yanghui Ye,Shihua Wu,Cen Yan,Jianwei Zhang,Zhe Zhao,Nusratgul Anwar,Yanfang Nie,Xuming Mao,Min Wu,Ran Zhang,Jidong Wang

doi:10.3389/fmicb.2020.01464

Abstract

Strain HM190, a moderate halophile, was isolated from rhizosphere soil of the mangrove Kandelia obovata in Fugong village, China. The 16S ribosomal RNA (rRNA) gene sequence and the results of phylogenetic analysis revealed that strain HM190 belonged to the genus Streptomyces and had the highest sequence similarity of 99.79% to Streptomyces heilongjiangensis NEAU-W2T. The complete genome of strain HM190 comprised 7,762,826 bp in a linear chromosome with 71.97% G + C content. According to antiSMASH analysis, a total of 30 biosynthetic gene clusters (BGCs) were predicted to be involved in secondary metabolism, 12 of which were responsible for the production of polyketide- and non-ribosomal peptide-derived secondary metabolites. Gene cluster 5 was responsible for macrolide biosynthesis in a strain-specific 126,331-bp genomic island belonging to the left-arm region. Combined genomics–metabolomics analysis led to the discovery of three 22-membered macrolides (compounds 1–3). Their structures were elucidated by using spectroscopic techniques including high-resolution electrospray ionization mass spectroscopy (HRESIMS) and nuclear magnetic resonance (NMR). The absolute configurations of compounds 1–3 were determined by the X-ray single crystal diffraction and NMR data analysis. All three compounds displayed moderate cytotoxic activities toward tumor cell lines HepG2, A549, and HCT116.

Highlights

Mangrove ecosystems cover about 60–75% of the world’s tropical and subtropical coastlines and grow in saline coastal sediment habitats at transition zones with ocean, fresh water, and land (Holguin et al, 2001)
The results of the analysis indicated that the isolate belonged to the genus Streptomyces and showed the highest sequence similarities to Streptomyces heilongjiangensis NEAUW2T (99.79%) and Streptomyces neyagawaensis NRRL B-3092T (99.59%)
In the phylogenetic analysis based on a neighborjoining tree (Figure 2), strain HM190 fell within the cluster of the genus Streptomyces and formed a coherent clade with S. heilongjiangensis NEAU-W2T

Summary

Introduction

Mangrove ecosystems cover about 60–75% of the world’s tropical and subtropical coastlines and grow in saline coastal sediment habitats at transition zones with ocean, fresh water, and land (Holguin et al, 2001). At the time of writing, 854 Streptomyces species with validly published names had been proposed according to List of Prokaryotic names with Standing in Nomenclature1 Some of these Streptomyces strains have been isolated from a wide range of marine habitats, including mangroves (Yan et al, 2010), marine sediments (Zhao et al, 2009), seawater (Zhu et al, 2011), sponges (Huang et al, 2016), algae (Girão et al, 2019), and corals (Alfredo et al, 2017). Since the first complete genome of Streptomyces coelicolor A3(2) was sequenced and reported in Bentley et al (2002), increasing numbers of Streptomyces genomes have been sequenced and deposited in public databases in recent years (Studholme, 2016), which has led to an increase in genomics–metabolomics studies of this genus (Xu et al, 2019). The number of complete genomes of Streptomyces has been limited because of their high G + C content, which results in shorter reads and much higher error rates during genome sequencing (Ioanna et al, 2012; Zhong et al, 2013)

Methods

Results

Conclusion