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Biosynthesis and incorporation of an alkylproline-derivative (APD) precursor into complex natural products
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SYSNO ASEP 0499560 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Biosynthesis and incorporation of an alkylproline-derivative (APD) precursor into complex natural products Author(s) Janata, Jiří (MBU-M) RID, ORCID
Kameník, Zdeněk (MBU-M) RID, ORCID
Gažák, Radek (MBU-M) RID, ORCID
Kadlčík, Stanislav (MBU-M) RID, ORCID
Najmanová, Lucie (MBU-M) RIDSource Title Natural Product Reports. - : Royal Society of Chemistry - ISSN 0265-0568
Roč. 35, č. 3 (2018), s. 257-289Number of pages 33 s. Language eng - English Country GB - United Kingdom Keywords synthetase adenylation domains ; marine-derived actinomycete ; peptidyl transferase center Subject RIV EE - Microbiology, Virology OECD category Microbiology R&D Projects GJ17-13436Y GA ČR - Czech Science Foundation (CSF) LQ1604 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) ED1.1.00/02.0109 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Institutional support MBU-M - RVO:61388971 UT WOS 000435987200004 EID SCOPUS 85044304765 DOI 10.1039/c7np00047b Annotation This review covers the biosynthetic and evolutionary aspects of lincosamide antibiotics, antitumour pyrrolobenzodiazepines (PBDs) and the quorum-sensing molecule hormaomycin. These structurally and functionally diverse groups of complex natural products all incorporate rarely occurring 4-alkyl-L-proline derivatives (APDs) biosynthesized from L-tyrosine through an unusual specialized pathway catalysed by a common set of six proteins named Apd1-Apd6. We give an overview of APD formation, which involves unusual enzyme activities, and its incorporation, which is based either on nonribosomal peptide synthetase (PBDs, hormaomycin) or a unique hybrid ergothioneine-dependent condensation system followed by mycothiol-dependent sulphur atom incorporation (lincosamides). Furthermore, within the public databases, we identified 36 novel unannotated biosynthetic gene clusters that putatively encode the biosynthesis of APD compounds. Their products presumably include novel PBDs, but also novel classes of APD compounds, indicating an unprecedented potential for the diversity enhancement of these functionally versatile complex metabolites. In addition, phylogenetic analysis of known and novel gene clusters for the biosynthesis of APD compounds allowed us to infer novel evolutionary hypotheses: Apd3 methyltransferase originates from a duplication event in a hormaomycin biosynthetic gene cluster ancestor, while putative Apd5 isomerase is evolutionarily linked to PhzF protein from the biosynthesis of phenazines. Lastly, we summarize the achievements in preparing hybrid APD compounds by directing their biosynthesis, and we propose that the number of nature-like APD compounds could by multiplied by replacing L-proline residues in various groups of complex metabolites with APD, i.e. by imitating the natural process that occurs with lincosamides and PBDs, in which the replacement of L-proline for APD has proved to be an evolutionary successful concept. Workplace Institute of Microbiology Contact Eliška Spurná, eliska.spurna@biomed.cas.cz, Tel.: 241 062 231 Year of Publishing 2019
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