Norine: A powerful resource for novel nonribosomal peptide discovery

Since its first release in 2008,Norine remains the unique resource completely devoted to nonribosomal peptides(NRPs).They are very attractive microbial secondary metabolites,displaying a remarkable diversity of structure and functions.Norine(http://bioinfo.lifl.fr/NRP)includes a database now containing more than 1160 annotated peptides and user-friendly interfaces enabling the querying of the database,through the annotations or the structure of the peptides.Dedicated tools are associated for structural comparison of the compounds and prediction of their biological activities.In this paper,we start by describing the knowledgebase and the dedicated tools.We then present some user cases to show how useful Norine is for the discovery of novel nonribosomal peptides.

In silico methods for linking genes and secondary metabolites: The way forward

In silico methods for linking genomic space to chemical space have played a crucial role in genomics driven discovery of new natural products as well as biosynthesis of altered natural products by engineering of biosynthetic pathways.Here we give an overview of available computational tools and then briefly describe a novel computational framework,namely retro-biosynthetic enumeration of biosynthetic reactions,which can add to the repertoire of computational tools available for connecting natural products to their biosynthetic gene clusters.Most of the currently available bioinformatics tools for analysis of secondary metabolite biosynthetic gene clusters utilize the“Genes to Metabolites”approach.In contrast to the“Genes to Metabolites”approach,the“Metabolites to Genes”or retro-biosynthetic approach would involve enumerating the various biochemical transformations or enzymatic reactions which would generate the given chemical moiety starting from a set of precursor molecules and identifying enzymatic domains which can potentially catalyze the enumerated biochemical transformations.In this article,we first give a brief overview of the presently available in silico tools and approaches for analysis of secondary metabolite biosynthetic pathways.We also discuss our preliminary work on development of algorithms for retro-biosynthetic enumeration of biochemical transformations to formulate a novel computational method for identifying genes associated with biosynthesis of a given polyketide or nonribosomal peptide.

Cell-free synthetic biology for in vitro biosynthesis of pharmaceutical natural products

Natural products with significant biological activities continuously act as rich sources for drug discovery and development.To harness the potential of these valuable compounds,robust methods need to be developed for their rapid and sustainable production.Cell-free biosynthesis of pharmaceutical natural products by in vitro reconstruction of the entire biosynthetic pathways represents one such solution.In this review,we focus on in vitro biosynthesis of two important classes of natural products,polyketides(PKs)and nonribosomal peptides(NRPs).First,we summarize purified enzyme-based systems for the biosynthesis of PKs,NRPs,and PK/NRP hybrids.Then,we introduce the cell-free protein synthesis(CFPS)-based technology for natural product production.With that,we discuss challenges and opportunities of cell-free synthetic biology for in vitro biosynthesis of natural products.