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

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

doi:10.3389/fchem.2020.00270

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

Front Chem. 2020 Apr 21:8:270. doi: 10.3389/fchem.2020.00270. eCollection 2020.

Authors

Lu Wang¹, Xianyan Zhang¹, Kaijin Zhang¹, Xiaomin Zhang¹, Tianjiao Zhu¹, Qian Che¹, Guojian Zhang^{1

2}, Dehai Li^{1

2}

Affiliations

¹ Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao, China.
² Laboratory for Marine Drugs and Bioproducts, Pilot National Laboratory for Marine Science and Technology, Qingdao, China.

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.

Keywords: Penicillium brocae; fumigatin chlorohydrin; genome mining; global regulator PbrlaeA; overexpression; polyketide; silent gene cluster.