Overexpression of Global Regulator PbrlaeA Leads to the Discovery of New Polyketide in Fungus Penicillium Brocae HDN-12-143.

Lu Wang,Tianjiao Zhu,Dehai Li,Xiaomin Zhang,Kaijin Zhang,Guojian Zhang,Qian Che,Xianyan Zhang

doi:10.3389/fchem.2020.00270

Abstract

Overexpression of the PbrlaeA gene of the fungus Penicillium brocae HDN-12-143 resulted in the isolation of four compounds including fumigatin chlorohydrin (1), whose configuration has not been reported before, and one new compound iso-fumigatin chlorohydrin (2). All structures including absolute configurations were elucidated on the basis of comprehensive spectroscopic data, 13C NMR calculations, and ECD calculations. Compounds 1 and 2 exhibited cytotoxic activity against HL-60 with IC50 of 18.63 and 24.83 μM.

Highlights

LaeA is a broad-domain factor that can regulate the production of secondary metabolites (Keller et al, 2006; Kosalkova et al, 2009; Sarikaya et al, 2010)
After being fermented with PDB medium under shaking condition at 28◦C for 9 days, the high performance liquid chromatography (HPLC) analysis of the extract of the OE::PbrlaeA mutant strain showed a series of new peaks compared with the extract of the wild type P. brocae HDN12-143 strain (Figure 1), which indicated the production of new secondary metabolites
Four compounds were isolated from the fungus Penicillium brocae HDN-12-143 by overexpression of the LaeA family gene of PbrlaeA

Summary

Introduction

LaeA is a broad-domain factor that can regulate the production of secondary metabolites (Keller et al, 2006; Kosalkova et al, 2009; Sarikaya et al, 2010). Overexpression of LaeA can enhance, or activate, the expression of gene clusters and produce new secondary metabolites (Jiang et al, 2016). During our recent work within the scope of exploring chemical diversity of fungal strains using tools manipulating the LaeA factor, the fungus Penicillium brocae HDN-12-143, isolated from sediment collected in the South China Sea, was selected as a candidate host to overexpress the LaeA gene due to its simple secondary metabolites background in comparison with its rich biosynthetic gene clusters, defined on the basis of bioinformatic analysis from the genome sequence, which shows a promising potential for secondary metabolite production (Figure S2). We will report the biosynthetic pathway activation by overexpression of global regulator PbrLaeA, the isolation and characterization of resulting compounds, as well as the biological activity evaluation results

Methods

Results

Conclusion