Surfactin biosynthesis

The PKS TE from erythromycin biosynthesis and the NRPS TE from surfactin biosynthesis are remarkably similar in three-dimensional topology (Figure 7.3) [42, 43]. It is expected that the application of enzyme-directed evolution will be able to further broaden the synthehc applications of TEs by increasing their activity and stability [44]. 

D Souia C, Nakano MM, Frisby DL, Zuber P. Translation of the open reading frame encoded by eomS, a gene of the srf operon, is necessary for the development of genetic competence but not surfactin biosynthesis in Bacillus subtib s. J Bacteriol 1995 177 4144-4148. 

Sen R. Surfactin biosynthesis, genetics and potential apphcations. Adv Exp Med Biol 2010 672 316-23. Heerklotz H, Seelig J. Detergent-like action of the antibiotic peptide surfactin on hpid membranes. Biophys J 2001 81 1547-54. 

Sen, R. Surfactin biosynthesis, genetics and potential applications. In Biosurfactants, Sen, R., Ed., Landes Bioscience Austin, Texas, 2010, pp. 316-323. 

Bacillussubtilis produces the cyclic peptide antibiotic surfactin (82).This is an acyl-pep-tidolactone composed of a p-hydroxy fatty acid side chain and seven amino acid residues, including a leucine at position 7. The biosynthesis of surfactin is catalyzed by a peptide synthetase consisting of three modules. The first and second modules are carrying three domains, the last module just one domain. The last domain catalyzes the activation and... 

Kluge, B. et al., Studies on the biosynthesis of surfactin, a lipopeptide antibiotic from Bacillus subtilis ATCC 21332, FEES Lett, 231, 107, 1988. 

Nakano MM, Marahiel MA, Zuber P. Identification of a genetic locus required for biosynthesis of the lipopeptide antibiotic surfactin in Bacillus subtilis. J Bacteriol 1988 170 5662-5668. 

It is noteworthy that nonribosomal peptide synthetase is similarly posttrans-lationally modified by covalent attachment of the 4 -phosphopantetheine group to the peptidyl carrier protein (PCP) [193-198]. While the ACPS can modify various apo-ACPs [167,173,187-189,191,192],it failed to modify PCPs from a variety of peptide synthetases [189]. This led to the discovery of the second family of PPTases [189], such as EntD from E. coli [189, 199, 200], Sfp from Bacillus subtilis [189,200-204], PptT from M. tuberculosis [264], and Gsp from B. brevis [ 189,205,206], required for the biosynthesis of enterobactin, surfactin, mycobactin, and gramicidin S, respectively. In contrast to ACPS, proteins in the latter family, such as Sfp, showed broader substrate specificity, modifying apo-PCPs, apo-ACPs, as well as apo-aryl carrier proteins and utilizing both CoA, acyl CoAs, and CoA analogs [204]. 

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