A chromatogram-simplified Streptomyces albus host for heterologous production of natural products

Antonie Van Leeuwenhoek. 2020 Apr;113(4):511-520. doi: 10.1007/s10482-019-01360-x. Epub 2019 Nov 28.

Abstract

Cloning natural product biosynthetic gene clusters from cultured or uncultured sources and their subsequent expression by genetically tractable heterologous hosts is an essential strategy for the elucidation and characterisation of novel microbial natural products. The availability of suitable expression hosts is a critical aspect of this workflow. In this work, we mutagenised five endogenous biosynthetic gene clusters from Streptomyces albus S4, which reduced the complexity of chemical extracts generated from the strain and eliminated antifungal and antibacterial bioactivity. We showed that the resulting quintuple mutant can express foreign biosynthetic gene clusters by heterologously producing actinorhodin, cinnamycin and prunustatin. We envisage that our strain will be a useful addition to the growing suite of heterologous expression hosts available for exploring microbial secondary metabolism.

Keywords: Heterologous expression; Natural products; Secondary metabolites; Streptomyces; Streptomyces albus.

MeSH terms

  • Anthraquinones / chemistry
  • Anthraquinones / metabolism
  • Bacteriocins / chemistry
  • Bacteriocins / metabolism
  • Biological Products / metabolism*
  • Cloning, Molecular
  • Gene Expression Regulation, Bacterial
  • Macrolides / chemistry
  • Macrolides / metabolism
  • Molecular Structure
  • Organic Chemicals / chemistry
  • Organic Chemicals / metabolism
  • Peptides, Cyclic / chemistry
  • Peptides, Cyclic / metabolism
  • Species Specificity
  • Streptomyces / metabolism*

Substances

  • Anthraquinones
  • Bacteriocins
  • Biological Products
  • Macrolides
  • Organic Chemicals
  • Peptides, Cyclic
  • prunustatin A
  • cinnamycin
  • neoantimycin
  • actinorhodin

Supplementary concepts

  • Streptomyces albus