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. Author manuscript; available in PMC: 2017 Aug 27.
Published in final edited form as: Nat Prod Rep. 2016 Apr 13;33(8):963–987. doi: 10.1039/c6np00017g

Table 1.

Comparison between different heterologous host systems for bacterial natural product biosynthesis.

Heterologous host Advantages Disadvantages
E. coli (Gram-negative)
  • Fast growth rate

  • Extensive genetic tools

  • Clean chemical background for downstream natural product detection and separation

  • Comprehensive knowledge of native metabolic networks

  • Lacks necessary biosynthetic machinery and precursors

  • Extensive genetic manipulation may be required for production of actinomycete natural products

P. putida (Gram-negative)
  • Fast growth rate

  • Well-developed genetic tools

  • Good adaptability to different physicochemical and nutritional conditions

  • Good xenobiotics tolerance

  • High NADPH regeneration rate

  • Versatile intrinsic metabolism with diverse enzymatic capacities

  • Low productivity yield of PKs/NRPs

  • Lack of advanced expression strategies for large BGCS

  • Limited knowledge of native metabolic networks

B. subtilis (Gram-positive)
  • Fast growth rate

  • Thorough genetic characterization

  • Well-developed recombinant methods

  • Suitable host for a wide assortment of biologically active small molecules from Bacillus spp.

  • Lack of autonomous plasmids to facilitate cloning, transfer and heterologous expression of large BGCs

Streptomyces spp.- (Gram-positive)
  • Rich in metabolic precursors and enzymatic mechanisms supporting most biosynthetic pathways

  • Versatile intrinsic metabolism supporting unique posttranslational modifications required for PKS and NRPS function

  • Suitable for expression of most proteins from actinomycetes

  • Slow growth rate

  • Lack of genetic parts and advanced genetic manipulation tools

  • Endogenous competing BGCs