Copper(II) and Zinc(II) Complexes with Bacterial Prodigiosin Are Targeting Site III of Bovine Serum Albumin and Acting as DNA Minor Groove Binders

Int J Mol Sci. 2024 Aug 1;25(15):8395. doi: 10.3390/ijms25158395.

Abstract

The negative environmental and social impacts of food waste accumulation can be mitigated by utilizing bio-refineries' approach where food waste is revalorized into high-value products, such as prodigiosin (PG), using microbial bioprocesses. The diverse biological activities of PG position it as a promising compound, but its high production cost and promiscuous bioactivity hinder its wide application. Metal ions can modulate the electronic properties of organic molecules, leading to novel mechanisms of action and increased target potency, while metal complex formation can improve the stability, solubility and bioavailability of the parent compound. The objectives of this study were optimizing PG production through bacterial fermentation using food waste, allowing good quantities of the pure natural product for further synthesizing and evaluating copper(II) and zinc(II) complexes with it. Their antimicrobial and anticancer activities were assessed, and their binding affinity toward biologically important molecules, bovine serum albumin (BSA) and DNA was investigated by fluorescence emission spectroscopy and molecular docking. The yield of 83.1 mg/L of pure PG was obtained when processed meat waste at 18 g/L was utilized as the sole fermentation substrate. The obtained complexes CuPG and ZnPG showed high binding affinity towards target site III of BSA, and molecular docking simulations highlighted the affinity of the compounds for DNA minor grooves.

Keywords: DNA interactions; Serratia marcescens; bio-refinery; metal complexation; prodigiosin; protein interactions; waste.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Binding Sites
  • Cattle
  • Coordination Complexes* / chemistry
  • Coordination Complexes* / pharmacology
  • Copper* / chemistry
  • Copper* / metabolism
  • DNA* / chemistry
  • DNA* / metabolism
  • Humans
  • Molecular Docking Simulation*
  • Prodigiosin* / chemistry
  • Prodigiosin* / metabolism
  • Prodigiosin* / pharmacology
  • Serum Albumin, Bovine* / chemistry
  • Serum Albumin, Bovine* / metabolism
  • Zinc* / chemistry
  • Zinc* / metabolism

Substances

  • Prodigiosin
  • Copper
  • Zinc
  • Serum Albumin, Bovine
  • DNA
  • Coordination Complexes
  • Antineoplastic Agents