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Biocombinatorial Synthesis of Novel Lipopeptides by COM Domain-Mediated Reprogramming of the Plipastatin NRPS Complex

Both donors and acceptors of communication-mediating (COM) domains are essential for coordinating intermolecular communication within nonribosomal peptides synthetases (NRPSs) complexes. Different sets of COM domains provide selectivity, allowing NRPSs to utilize different natural biosynthetic templ...

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Autores principales: Liu, Hongxia, Gao, Ling, Han, Jinzhi, Ma, Zhi, Lu, Zhaoxin, Dai, Chen, Zhang, Chong, Bie, Xiaomei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5112269/
https://www.ncbi.nlm.nih.gov/pubmed/27909427
http://dx.doi.org/10.3389/fmicb.2016.01801
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author Liu, Hongxia
Gao, Ling
Han, Jinzhi
Ma, Zhi
Lu, Zhaoxin
Dai, Chen
Zhang, Chong
Bie, Xiaomei
author_facet Liu, Hongxia
Gao, Ling
Han, Jinzhi
Ma, Zhi
Lu, Zhaoxin
Dai, Chen
Zhang, Chong
Bie, Xiaomei
author_sort Liu, Hongxia
collection PubMed
description Both donors and acceptors of communication-mediating (COM) domains are essential for coordinating intermolecular communication within nonribosomal peptides synthetases (NRPSs) complexes. Different sets of COM domains provide selectivity, allowing NRPSs to utilize different natural biosynthetic templates. In this study, novel lipopeptides were synthesized by reprogramming the plipastatin biosynthetic machinery. A Thr-to-Asp point mutation was sufficient to shift the selectivity of the donor COM domain of ppsB toward that of ppsD. Deletion and/or interchangeability established donor and acceptor function. Variations in acceptor COM domain did not result in novel product formation in the presence of its partner donor, whereas plipastatin formation was completely abrogated by altering donor modules. Five novel lipopeptides (cyclic pentapeptide, linear hexapeptide, nonapeptide, heptapeptide, and cyclic octapeptide) were identified and verified by high-resolution LC-ESI-MS/MS. In addition, we demonstrated the potential to generate novel strains with the antimicrobial activity by selecting compatible COM domains, and the novel lipopeptides exhibited antimicrobial activity against five of the fungal species at a contention of 31.25–125 μg/ml.
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spelling pubmed-51122692016-12-01 Biocombinatorial Synthesis of Novel Lipopeptides by COM Domain-Mediated Reprogramming of the Plipastatin NRPS Complex Liu, Hongxia Gao, Ling Han, Jinzhi Ma, Zhi Lu, Zhaoxin Dai, Chen Zhang, Chong Bie, Xiaomei Front Microbiol Microbiology Both donors and acceptors of communication-mediating (COM) domains are essential for coordinating intermolecular communication within nonribosomal peptides synthetases (NRPSs) complexes. Different sets of COM domains provide selectivity, allowing NRPSs to utilize different natural biosynthetic templates. In this study, novel lipopeptides were synthesized by reprogramming the plipastatin biosynthetic machinery. A Thr-to-Asp point mutation was sufficient to shift the selectivity of the donor COM domain of ppsB toward that of ppsD. Deletion and/or interchangeability established donor and acceptor function. Variations in acceptor COM domain did not result in novel product formation in the presence of its partner donor, whereas plipastatin formation was completely abrogated by altering donor modules. Five novel lipopeptides (cyclic pentapeptide, linear hexapeptide, nonapeptide, heptapeptide, and cyclic octapeptide) were identified and verified by high-resolution LC-ESI-MS/MS. In addition, we demonstrated the potential to generate novel strains with the antimicrobial activity by selecting compatible COM domains, and the novel lipopeptides exhibited antimicrobial activity against five of the fungal species at a contention of 31.25–125 μg/ml. Frontiers Media S.A. 2016-11-17 /pmc/articles/PMC5112269/ /pubmed/27909427 http://dx.doi.org/10.3389/fmicb.2016.01801 Text en Copyright © 2016 Liu, Gao, Han, Ma, Lu, Dai, Zhang and Bie. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Liu, Hongxia
Gao, Ling
Han, Jinzhi
Ma, Zhi
Lu, Zhaoxin
Dai, Chen
Zhang, Chong
Bie, Xiaomei
Biocombinatorial Synthesis of Novel Lipopeptides by COM Domain-Mediated Reprogramming of the Plipastatin NRPS Complex
title Biocombinatorial Synthesis of Novel Lipopeptides by COM Domain-Mediated Reprogramming of the Plipastatin NRPS Complex
title_full Biocombinatorial Synthesis of Novel Lipopeptides by COM Domain-Mediated Reprogramming of the Plipastatin NRPS Complex
title_fullStr Biocombinatorial Synthesis of Novel Lipopeptides by COM Domain-Mediated Reprogramming of the Plipastatin NRPS Complex
title_full_unstemmed Biocombinatorial Synthesis of Novel Lipopeptides by COM Domain-Mediated Reprogramming of the Plipastatin NRPS Complex
title_short Biocombinatorial Synthesis of Novel Lipopeptides by COM Domain-Mediated Reprogramming of the Plipastatin NRPS Complex
title_sort biocombinatorial synthesis of novel lipopeptides by com domain-mediated reprogramming of the plipastatin nrps complex
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5112269/
https://www.ncbi.nlm.nih.gov/pubmed/27909427
http://dx.doi.org/10.3389/fmicb.2016.01801
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