Polyketide and nonribosomal peptide retro-biosynthesis and global gene cluster matching.
Nat Chem Biol
; 12(12): 1007-1014, 2016 Dec.
Article
em En
| MEDLINE
| ID: mdl-27694801
ABSTRACT
Polyketides (PKs) and nonribosomal peptides (NRPs) are profoundly important natural products, forming the foundations of many therapeutic regimes. Decades of research have revealed over 11,000 PK and NRP structures, and genome sequencing is uncovering new PK and NRP gene clusters at an unprecedented rate. However, only â¼10% of PK and NRPs are currently associated with gene clusters, and it is unclear how many of these orphan gene clusters encode previously isolated molecules. Therefore, to efficiently guide the discovery of new molecules, we must first systematically de-orphan emergent gene clusters from genomes. Here we provide to our knowledge the first comprehensive retro-biosynthetic program, generalized retro-biosynthetic assembly prediction engine (GRAPE), for PK and NRP families and introduce a computational pipeline, global alignment for natural products cheminformatics (GARLIC), to uncover how observed biosynthetic gene clusters relate to known molecules, leading to the identification of gene clusters that encode new molecules.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Peptídeos
/
Família Multigênica
/
Biossíntese de Peptídeos Independentes de Ácido Nucleico
/
Policetídeos
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Nat Chem Biol
Assunto da revista:
BIOLOGIA
/
QUIMICA
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Canadá