Genetic engineering of Bacillus subtilis for the commercial production of riboflavin

  • J B Perkins
  • A Sloma
  • T Hermann
  • K Theriault
  • E Zachgo
  • T Erdenberger
  • N Hannett
  • N P Chatterjee
  • V Williams II
  • GA Rufo Jr
  • R Hatch
  • J Pero

Recombinant DNA engineering was combined with mutant selection and fermentation improvement to develop a strain of Bacillus subtilis that produces commercially attractive levels of riboflavin. The B. subtilis riboflavin production strain contains multiple copies of a modified B. subtilis riboflavin biosynthetic operon (rib operon) integrated at two different sites in the B. subtilis chromosome. The modified rib operons are expressed constitutively from strong phage promoters located at the 5′ end and in an internal region of the operon. The engineered strain also contains purine analog-resistant mutations designed to deregulate the purine pathway (GTP is the precursor for riboflavin), and a riboflavin analog-resistant mutation in ribC that deregulates the riboflavin biosynthetic pathway.

Keywords: riboflavin; metabolic engineering; Bacillus subtilis 

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Copyright information

© Society for Industrial Microbiology 1999

Authors and Affiliations

  • J B Perkins
    • 1
  • A Sloma
    • 2
  • T Hermann
    • 2
  • K Theriault
    • 2
  • E Zachgo
    • 2
  • T Erdenberger
    • 2
  • N Hannett
    • 2
  • N P Chatterjee
    • 1
  • V Williams II
    • 2
  • GA Rufo Jr
    • 2
  • R Hatch
    • 2
  • J Pero
    • 1
  1. 1.OmniGene Bioproducts, 763D Concord Ave, Cambridge, MA 02138, USAUS
  2. 2.BioTechnica International, Cambridge, MA, USAUS

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