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Applied and Environmental Microbiology, November 2008, p. 6591-6597, Vol. 74, No. 21
0099-2240/08/$08.00+0     doi:10.1128/AEM.01334-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Mechanistic Dissection of the Enzyme Complexes Involved in Biosynthesis of Lacticin 3147 and Nisin {triangledown} ,{dagger}

Anneke Kuipers, Jenny Meijer-Wierenga, Rick Rink, Leon D. Kluskens, and Gert N. Moll*

BiOMaDe Technology Foundation, Nijenborgh 4, 9747 AG Groningen, The Netherlands

Received 14 June 2008/ Accepted 6 September 2008

The thioether rings in the lantibiotics lacticin 3147 and nisin are posttranslationally introduced by dehydration of serines and threonines, followed by coupling of these dehydrated residues to cysteines. The prepeptides of the two-component lantibiotic lacticin 3147, LtnA1 and LtnA2, are dehydrated and cyclized by two corresponding bifunctional enzymes, LtnM1 and LtnM2, and are subsequently processed and exported via one bifunctional enzyme, LtnT. In the nisin synthetase complex, the enzymes NisB, NisC, NisT, and NisP dehydrate, cyclize, export, and process prenisin, respectively. Here, we demonstrate that the combination of LtnM2 and LtnT can modify, process, and transport peptides entirely different from LtnA2 and that LtnT can process and transport unmodified LtnA2 and unrelated peptides. Furthermore, we demonstrate a higher extent of NisB-mediated dehydration in the absence of thioether rings. Thioether rings apparently inhibited dehydration, which implies alternating actions of NisB and NisC. Furthermore, certain (but not all) NisC-cyclized peptides were exported with higher efficiency as a result of their conformation. Taken together, these data provide further insight into the applicability of Lactococcus lactis strains containing lantibiotic enzymes for the design and production of modified peptides.

* Corresponding author. Mailing address: BiOMaDe Technology Foundation, Nijenborgh 4, 9747 AG Groningen, The Netherlands. Phone: 31 50 3638070. Fax: 31 50 3634429. E-mail: Moll{at}biomade.nl

{triangledown} Published ahead of print on 12 September 2008.

{dagger} Supplemental material for this article may be found at http://aem.asm.org/.

Applied and Environmental Microbiology, November 2008, p. 6591-6597, Vol. 74, No. 21
0099-2240/08/$08.00+0     doi:10.1128/AEM.01334-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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