| Форма представления | Статьи в зарубежных журналах и сборниках |
| Год публикации | 2019 |
| Язык | английский |
|
Тропша Александр , автор
|
|
Блейх Рейчел , автор
Фараг Шериф Хуссейн , автор
Шенк Элизабет , автор
|
| Библиографическое описание на языке оригинала |
Tropsha A. Inter-Modular Linkers play a crucial role in governing the biosynthesis of non-ribosomal peptides / S. Farag, R.M. Bleich, E.A. Shank, O. Isayev, A.A. Bowers, A. Tropshа // BIOINFORMATICS. - 2019. - Т. 35 (19). - р. 3584-3591.
|
| Аннотация |
Motivation: Non-ribosomal peptide synthetases (NRPSs) are modular enzymatic machines that catalyze the ribosome-independent production of structurally complex small peptides, many of which have important clinical applications as antibiotics, antifungals and anti-cancer agents. Several groups have tried to expand natural product diversity by intermixing different NRPS modules to create synthetic peptides. This approach has not been as successful as anticipated, suggesting that these modules are not fully interchangeable.
Results: We explored whether Inter-Modular Linkers (IMLs) impact the ability of NRPS modules to communicate during the synthesis of NRPs. We developed a parser to extract 39 804 IMLs from both well annotated and putative NRPS biosynthetic gene clusters from 39 232 bacterial genomes and established the first IMLs database. We analyzed these IMLs and identified a striking relationship between IMLs and the amino acid substrates of their adjacent modules. More than 92% of the identified IMLs connect modules that activate a particular pair of substrates, suggesting that significant specificity is embedded within these sequences. We therefore propose that incorporating the correct IML is critical when attempting combinatorial biosynthesis of novel NRPS. |
| Ключевые слова |
COMBINATORIAL BIOSYNTHESIS; SYNTHETASE PROTEINS; DOMAIN LINKERS; POLYKETIDE; ANTIBIOTICS; DISSECTION; DAPTOMYCIN; PREDICTION; RESOURCE; REGIONS |
| Название журнала |
Bioinformatics
|
| URL |
https://apps.webofknowledge.com/full_record.do?product=WOS&search_mode=SourceByDais&qid=10&SID=E1yl6cKjP6VQawX9uwc&page=1&doc=2 |
| Пожалуйста, используйте этот идентификатор, чтобы цитировать или ссылаться на эту карточку |
https://repository.kpfu.ru/?p_id=220371 |
Полная запись метаданных  |
| Поле DC |
Значение |
Язык |
| dc.contributor.author |
Тропша Александр |
ru_RU |
| dc.contributor.author |
Блейх Рейчел |
ru_RU |
| dc.contributor.author |
Фараг Шериф Хуссейн |
ru_RU |
| dc.contributor.author |
Шенк Элизабет |
ru_RU |
| dc.date.accessioned |
2019-01-01T00:00:00Z |
ru_RU |
| dc.date.available |
2019-01-01T00:00:00Z |
ru_RU |
| dc.date.issued |
2019 |
ru_RU |
| dc.identifier.citation |
Tropsha A. Inter-Modular Linkers play a crucial role in governing the biosynthesis of non-ribosomal peptides / S. Farag, R.M. Bleich, E.A. Shank, O. Isayev, A.A. Bowers, A. Tropshа // BIOINFORMATICS. - 2019. - Т. 35 (19). - р. 3584-3591.
|
ru_RU |
| dc.identifier.uri |
https://repository.kpfu.ru/?p_id=220371 |
ru_RU |
| dc.description.abstract |
Bioinformatics |
ru_RU |
| dc.description.abstract |
Motivation: Non-ribosomal peptide synthetases (NRPSs) are modular enzymatic machines that catalyze the ribosome-independent production of structurally complex small peptides, many of which have important clinical applications as antibiotics, antifungals and anti-cancer agents. Several groups have tried to expand natural product diversity by intermixing different NRPS modules to create synthetic peptides. This approach has not been as successful as anticipated, suggesting that these modules are not fully interchangeable.
Results: We explored whether Inter-Modular Linkers (IMLs) impact the ability of NRPS modules to communicate during the synthesis of NRPs. We developed a parser to extract 39 804 IMLs from both well annotated and putative NRPS biosynthetic gene clusters from 39 232 bacterial genomes and established the first IMLs database. We analyzed these IMLs and identified a striking relationship between IMLs and the amino acid substrates of their adjacent modules. More than 92% of the identified IMLs connect modules that activate a particular pair of substrates, suggesting that significant specificity is embedded within these sequences. We therefore propose that incorporating the correct IML is critical when attempting combinatorial biosynthesis of novel NRPS. |
ru_RU |
| dc.language.iso |
ru |
ru_RU |
| dc.subject |
|
ru_RU |
| dc.title |
Inter-Modular Linkers play a crucial role in governing the biosynthesis of non-ribosomal peptides |
ru_RU |
| dc.type |
Статьи в зарубежных журналах и сборниках |
ru_RU |
|
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