Microbial Transformation of neo-Clerodane Diterpenoid, Scutebarbatine F, by Streptomyces sp. CPCC 205437

Dewu Zhang,Wuli Zhao,Wenxia Zhao,Xiaoyu Tao,Liyan Yu,Yujia Wang,Shengjun Dai,Guowei Gu,Yan Ren

doi:10.3389/fmicb.2021.662321

Abstract

Biotransformation of the neo-clerodane diterpene, scutebarbatine F (1), by Streptomyces sp. CPCC 205437 was investigated for the first time, which led to the isolation of nine new metabolites, scutebarbatine F1–F9 (2–10). Their structures were determined by extensive high-resolution electrospray ionization mass spectrometry (HRESIMS) and NMR data analyses. The reactions that occurred included hydroxylation, acetylation, and deacetylation. Compounds 2–4 and 8–10 possess 18-OAc fragment, which were the first examples of 13-spiro neo-clerodanes with 18-OAc group. Compounds 7–10 were the first report of 13-spiro neo-clerodanes with 2-OH. Compounds 1–10 were biologically evaluated for the cytotoxic, antiviral, and antibacterial activities. Compounds 5, 7, and 9 exhibited cytotoxic activities against H460 cancer cell line with inhibitory ratios of 46.0, 42.2, and 51.1%, respectively, at 0.3 μM. Compound 5 displayed a significant anti-influenza A virus activity with inhibitory ratio of 54.8% at 20 μM, close to the positive control, ribavirin.

Highlights

Biotransformation of natural products has been proved to be an efficient and environmentally friendly approach to the preparation of new compounds, and biotransformation is a powerful tool for the regioselective and stereoselective introduction under mild conditions (Bianchini et al, 2015; Cao et al, 2015; Hegazy et al, 2015; Zafar et al, 2016; Khojasteh et al, 2019)
The 13C NMR and distortionless enhancement by polarization transfer (DEPT) spectra of 2 showed 20 typical carbon signals for neo-clerodane diterpene skeleton, which consisted of three methyl carbons, six methylene carbons, five methine carbons, and six quaternary carbons
Compounds 1–10 were evaluated for cytotoxic activities against five human cancer cell lines including H460, HCT8, HT15, H1975, and MIA-PaCa-2

Summary

Introduction

Biotransformation of natural products has been proved to be an efficient and environmentally friendly approach to the preparation of new compounds, and biotransformation is a powerful tool for the regioselective and stereoselective introduction under mild conditions (Bianchini et al, 2015; Cao et al, 2015; Hegazy et al, 2015; Zafar et al, 2016; Khojasteh et al, 2019). All of the natural clerodane diterpenes were classified as seven different types on the basis of the decalin ring and C-11–C-16 moiety (Supplementary Figure 1; Li et al, 2016). To the best of our knowledge, there is no report about biotransformation of 13-spiro neo-clerodane diterpenes till now. Scutebarbatine F (1) with 13-spiro neo-clerodane skeleton was firstly isolated from Scutellaria barbata in 2006 by Dai group and showed significant cytotoxic activities against HONE1 nasopharyngeal, KB oral epidermoid carcinoma, and HT29 colorectal carcinoma cell lines (Dai et al, 2006). In an attempt to obtain new biologically active neo-clerodane diterpenoids. We describe the isolation, structure elucidation, and biological activities of nine biotransformation products (2–10)

Methods

Results

Conclusion