KFU. Card publication. Inter-Modular Linkers play a crucial role in governing the biosynthesis of non-ribosomal peptides

KAZAN
FEDERAL UNIVERSITY

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INTER-MODULAR LINKERS PLAY A CRUCIAL ROLE IN GOVERNING THE BIOSYNTHESIS OF NON-RIBOSOMAL PEPTIDES

Form of presentation

Articles in international journals and collections

Year of publication

2019

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Authors, employees of KFU

Tropsha Aleksandr , author

Other authors

Bleykh Reychel , author

Farag Sherif Khusseyn , author

Shenk Elizabet , author

Bibliographic description in the original language

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. Tropsha // BIOINFORMATICS. - 2019. - T. 35 (19). - r. 3584-3591.

Annotation

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.

Keywords

COMBINATORIAL BIOSYNTHESIS; SYNTHETASE PROTEINS; DOMAIN LINKERS; POLYKETIDE; ANTIBIOTICS; DISSECTION; DAPTOMYCIN; PREDICTION; RESOURCE; REGIONS

The name of the journal

Bioinformatics

URL

https://apps.webofknowledge.com/full_record.do?product=WOS&search_mode=SourceByDais&qid=10&SID=E1yl6cKjP6VQawX9uwc&page=1&doc=2

Please use this ID to quote from or refer to the card

https://repository.kpfu.ru/eng/?p_id=220371&p_lang=2

Full metadata record

Field DC	Value	Language
dc.contributor.author	Tropsha Aleksandr	ru_RU
dc.contributor.author	Bleykh Reychel	ru_RU
dc.contributor.author	Farag Sherif Khusseyn	ru_RU
dc.contributor.author	Shenk Elizabet	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. Tropsh� // BIOINFORMATICS. - 2019. - �. 35 (19). - �. 3584-3591.	ru_RU
dc.identifier.uri	https://repository.kpfu.ru/eng/?p_id=220371&p_lang=2	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	Articles in international journals and collections	ru_RU