Protein secretion and possible roles for multiple signal peptidases for precursor processing in Bacilli

Sierd Bron, Albert Bolhuis, Harold Tjalsma, Siger Holsappel, Gerard Venema, Jan Maarten Van Dijl

Research output: Contribution to journalReview articlepeer-review

68 Citations (SciVal)


Bacillus subtilis is one of the best known Gram-positive bacteria at both the genetic and physiological level. The entire sequence of its chromosome is known and efficient tools for the genetic modification of this bacterium are available. Moreover, B. subtilis and related Bacillus species are widely used in biotechnology, in particular for the production of secreted enzymes. Although bacilli can secrete large amounts of several native enzymes, the use of these bacteria for the production of heterologous enzymes has frequently resulted in low yields. Here we describe the identification of several components of the Bacillus protein secretion machinery. These components can now be engineered for optimal protein secretion. Special emphasis is given on type I signal peptidases, which remove signal peptides from secretory precursor proteins. Five genes specifying such enzymes (sip, for signal peptidase) are present on the B. subtilis chromosome. Although none of the sip genes is essential by itself, a specific combination of mutations in these genes is lethal. The expression pattern of some of the sip genes coincides with that of many secretory proteins, which seems to reflect an adaptation to high demands on the secretion machinery. Although the various B. subtilis type I signal peptidases have at least partially overlapping substrate specificities, clear differences in substrate preferences are also evident. These observations have implications for the engineering of the processing apparatus for improved secretion of native and heterologous proteins by Bacillus.

Original languageEnglish
Pages (from-to)3-13
Number of pages11
JournalJournal of Biotechnology
Issue number1
Publication statusPublished - 17 Sept 1998


  • Bacillus subtilis
  • Cryptic plasmids
  • Gram-positives
  • Host-vector system
  • Secretion pathway
  • Signal peptidase

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology


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