Biosynthesis and incorporation of an alkylproline-derivative (APD) precursor into complex natural products
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388971%3A_____%2F18%3A00499560" target="_blank" >RIV/61388971:_____/18:00499560 - isvavai.cz</a>
Result on the web
<a href="http://dx.doi.org/10.1039/c7np00047b" target="_blank" >http://dx.doi.org/10.1039/c7np00047b</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1039/c7np00047b" target="_blank" >10.1039/c7np00047b</a>
Alternative languages
Result language
angličtina
Original language name
Biosynthesis and incorporation of an alkylproline-derivative (APD) precursor into complex natural products
Original language description
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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10606 - Microbiology
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2018
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Natural Product Reports
ISSN
0265-0568
e-ISSN
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Volume of the periodical
35
Issue of the periodical within the volume
3
Country of publishing house
GB - UNITED KINGDOM
Number of pages
33
Pages from-to
257-289
UT code for WoS article
000435987200004
EID of the result in the Scopus database
2-s2.0-85044304765