Protein–protein interactions in polyketide synthase–nonribosomal peptide synthetase hybrid assembly lines

Abstract

Covering: up to early 2018 Polyketides and nonribosomal peptides are two major families of natural product with a broad range of biological activities. Polyketide synthases (PKSs) assemble small acetic acid-type acyl building blocks into polyketides through C-C bonds, and nonribosomal peptide synthetases (NRPSs) assemble amino acids into peptides through amide bonds. PKS-NRPS hybrid assembly lines build structurally complex polyketide-amino acid/peptide hybrid molecules that incorporate both acyl and aminoacyl building blocks into their products. Their combined functionalities expand the biological activities of these molecules by mixing their chemical properties. Protein-protein interactions are necessary within PKS-NRPS hybrid assembly lines to achieve accurate linkage between the PKS and NRPS systems. This review summarizes the current understanding of the roles and importance of the protein-protein interactions in various PKS-NRPS hybrid assembly lines.

Nature's Combinatorial Biosynthesis Produces Vatiamides A–F

“…This occurs collinearly such that the order in which the genes are transcribed is coincident with the functioning of proteins that selectively interact to elongate NPs with high fidelity.The interface between modules occurs via interacting type Io rII docking domains (dd) between PKSs and communication (COM) domains between some NRPS modules. [9] At hird type of structurally distinct docking interaction between combinations of PKS and/or NRPS modules was characterized in tubulysin and rhabdopeptide/xenorpeptide (RXP) biosynthesis,a nd are referred to here as (C-terminus-Nterminus) b-abbaa type domains. [10][11][12] We used abioactivityand reactivity-guided approach to characterize six new lipopeptides and their biosynthetic pathway from the benthic cyanobacterium Moorea producens ASI6Jul14-2.…”

Draft genome analysis of antimicrobial Streptomyces isolated from Himalayan lichen

“…The lichens were vortexed for 1 min and the supernatant was discarded; this step was repeated twice. Then, 100-μl aliquots of the washed, broken lichen solution were spread on replicate plates containing MY media (3.0 g malt extract, 3.0 g yeast extract, 10.0 g peptone, 10.0 g dextrose, and 20.0 g agar, pH 7.2), R2A media (0.5 g proteose peptone, 0.5 g casamino acid, 0.5 g yeast extract, 0.5 g dextrose, 0.5 g soluble starch, 0.3 g sodium pyruvate, 0.3 g dipotassium phosphate, and 0.05 g magnesium sulfate, pH 7.2), or Bennett's media (10.0 g glucose, 1.0 g yeast extract, 2.0 g Bacto-peptone, and 1.0 g beef extract, pH 7.2); the plates were incubated at different temperatures (8,15,25, and 37°C) for 3 to 30 days.…”

“…Most research studies regarding lichen-associated bacteria are based on the hypothesis that such bacteria will produce one or more unusual secondary metabolites in the symbiotic relationship. The biosynthesis of secondary metabolites, analyzed by biosynthetic gene cluster, is already well known; this includes multidomain enzymes such as polyketide synthase (PKS) and non-ribosomal peptide synthetase (NRPS) [7][8][9][10]. Although PKS and NRPS comprise most of the metabolite class, knowledge regarding the biological activities of PKS and NRPS genes remains insufficient.…”

Nature's Combinatorial Biosynthesis Produces Vatiamides A–F

“…This occurs collinearly such that the order in which the genes are transcribed is coincident with the functioning of proteins that selectively interact to elongate NPs with high fidelity. The interface between modules occurs via interacting type I or II docking domains (dd) between PKSs and communication (COM) domains between some NRPS modules . A third type of structurally distinct docking interaction between combinations of PKS and/or NRPS modules was characterized in tubulysin and rhabdopeptide/xenorpeptide (RXP) biosynthesis, and are referred to here as (C‐terminus‐N‐terminus) β‐αββαα type domains .…”