Nonribosomal Peptide Biosynthesis: Point Mutations and Module Skipping Lead to Chemical Diversity

Abstract

Big effects from small changes: In a comparative analysis of the nonribosomal peptide synthetases (NRPSs) from the biosynthetic pathways of two highly related myxobacterial lipopeptides, module skipping and point mutations are directly correlated to structural variations in these natural products. The skipping process during myxochromide S biosynthesis was characterized biochemically and represents the first example of a module skipping in NRPS systems.

The unique DKxanthene secondary metabolite family from the myxobacterium Myxococcus xanthus is required for developmental sporulation

“…They are the first new family of secondary metabolites isolated from M. xanthus DK1622 after the recent description of myxochromides and myxovirescins (10,11), two well known classes of myxobacterial secondary metabolites, which had been described from other myxobacterial species (17,33).…”

Fungal cyclooligomerdepsipeptides: From classical biochemistry to combinatorial biosynthesis

“…(teleomorph: Leptosphaerulina spp.). The cyclotetradepsipeptide angolide 12 (5) and the cyclohexadepsipeptide sporidesmolides 13 (6) are apparent dimers of a dipeptidol (angolide) or a tripeptidol (sporidesmolides). However, the exclusive utilization of D amino acids in one half of these molecules, and L amino acids in the other half, argues against their origin from cyclodimerization (see Section 4.9).…”

“…In rare cases violations to this rule may be observed, for example as in module skipping. 5,6 In contrast, iterative (Type B) NRPSs use some of …”

“…2 Hydroxycarboxylic acid incorporation in bacterial vs. fungal NRPS systems 5. 3 Regulation and export 6 Heterologous expression of CODSs 6.1…”

Genome Mining of EndophyticStreptomyces wadayamensisReveals High Antibiotic Production Capability

“…The possibility to connect genes to natural products enables to direct the discovery of novel molecules, for instance, metabolites as coelichelin, 6 orfamide A 7 and salinilactam 8 were found by searching programs guided by the prediction of physical-chemical properties, anticipation of precursors incorporation, manipulation of higher levels and pathway specific regulators, inactivation of biosynthetic genes and analytical evaluation, and by in vitro reconstitution. [9][10][11][12][13][14][15][16][17][18] Driven by the current status of the genome to natural products programs we invested in the Whole Genome Shotgun project of Streptomyces wadayamensis A23, an endophytic strain isolated from Citrus reticulata (tangerine). 19 Biochemical qualitative tests showed that strain A23 inhibits the growth of Candida albicans pathogen, Bacillus megaterium, Neisseria meningitides strains, and multiresistant Staphylococcus aureus.…”