Marine Bacterial Aromatic Polyketides From Host-Dependent Heterologous Expression and Fungal Mode of Cyclization.

Chunshuai Huang,Changsheng Zhang,Yiguang Zhu,Chengshan Yuan,Chunfang Yang,Wenjun Zhang

doi:10.3389/fchem.2018.00528

Abstract

The structure diversity of type II polyketide synthases-derived bacterial aromatic polyketides is often enhanced by enzyme controlled or spontaneous cyclizations. Here we report the discovery of bacterial aromatic polyketides generated from 5 different cyclization modes and pathway crosstalk between the host and the heterologous fluostatin biosynthetic gene cluster derived from a marine bacterium. The discovery of new compound SEK43F (2) represents an unusual carbon skeleton resulting from a pathway crosstalk, in which a pyrrole-like moiety derived from the host Streptomyces albus J1074 is fused to an aromatic polyketide SEK43 generated from the heterologous fluostatin type II PKSs. The occurrence of a new congener, fluoquinone (3), highlights a bacterial aromatic polyketide that is exceptionally derived from a characteristic fungal F-mode first-ring cyclization. This study expands our knowledge on the power of bacterial type II PKSs in diversifying aromatic polyketides.

Highlights

IntroductionAromatic polyketides (APKs) comprise a rich class of natural products with diverse structures and exhibit antimicrobial, antitumor, antiparasitic, antiviral, and other activities (Shen, 2000; Hertweck et al, 2007; Das and Khosla, 2009; Zhou et al, 2010; Zhang Z. et al, 2017)
Most bacterial Aromatic polyketides (APKs) are synthesized by type II polyketide synthases (PKSs)
Upon a large scale fermentation of S. albus J1074/pCSG5033 (containing the intact fls gene cluster (Yang et al, 2015; Supplementary Figure 1) in a 40-L fermentator and the subsequent isolation with various chromatographic methods, FST C (1) was obtained as the major product, along with several new dimeric FSTs derived from non-enzymatic reactions (Huang et al, 2018)

Summary

Introduction

Aromatic polyketides (APKs) comprise a rich class of natural products with diverse structures and exhibit antimicrobial, antitumor, antiparasitic, antiviral, and other activities (Shen, 2000; Hertweck et al, 2007; Das and Khosla, 2009; Zhou et al, 2010; Zhang Z. et al, 2017). The “minimal” type II PKSs consist of a set of iteratively used enzymes including two ketosynthase units (KSα and KSβ) and an acyl-carrier protein (ACP) (Shen, 2000; Hertweck et al, 2007; Das and Khosla, 2009; Zhou et al, 2010; Zhang Z. et al, 2017). Shunt products are produced from the reactive poly-β-ketone chains by spontaneous and aberrant cyclization to further enhance the structural diversity of APKs (Shen, 2000; Hertweck et al, 2007; Das and Khosla, 2009; Zhou et al, 2010; Zhang Z. et al, 2017)

Methods

Results

Conclusion