Structural rearrangements of a polyketide synthase module during its catalytic cycle. A ketoreductase domain in the PksJ protein of the bacillaene assembly line carries out both alpha- and beta-ketone reduction during chain growth. The structural role of the carrier protein–active controller or passive carrier. Phylogenetic analysis of condensation domains in NRPS sheds light on their functional evolution. Rausch, C., Hoof, I., Weber, T., Wohlleben, W. Interrupted adenylation domains: unique bifunctional enzymes involved in nonribosomal peptide biosynthesis. Broad-host-range expression reveals native and host regulatory elements that influence heterologous antibiotic production in Gram-negative bacteria. putida KT2440 as an enhanced host for heterologous gene expression. A new large-DNA-fragment delivery system based on integrase activity from an integrative and conjugative element. Family-wide structural characterization and genomic comparisons decode the diversity-oriented biosynthesis of thalassospiramides by marine Proteobacteria. Biosynthetic multitasking facilitates thalassospiramide structural diversity in marine bacteria. Thalassospiramides A and B, immunosuppressive peptides from the marine bacterium Thalassospira sp. Iron acquisition in plague: modular logic in enzymatic biogenesis of yersiniabactin by Yersinia pestis.
The biosynthetic gene cluster for the antitumor drug bleomycin from Streptomyces verticillus ATCC15003 supporting functional interactions between nonribosomal peptide synthetases and a polyketide synthase. Deciphering tuberactinomycin biosynthesis: isolation, sequencing, and annotation of the viomycin biosynthetic gene cluster. Identification of the biosynthetic gene cluster and an additional gene for resistance to the antituberculosis drug capreomycin. Biosynthetic pathway for mannopeptimycins, lipoglycopeptide antibiotics active against drug-resistant gram-positive pathogens. Nonribosomal peptide synthesis-principles and prospects. Biosynthesis of polyketides by trans-AT polyketide synthases. Daptomycin, a bacterial lipopeptide synthesized by a nonribosomal machinery. Programming of erythromycin biosynthesis by a modular polyketide synthase. The structural biology of biosynthetic megaenzymes. Expanding bidirectional intermodule domain interactions could represent a viable mechanism for generating chemical diversity without increasing the size of biosynthetic assembly lines and challenges our understanding of the potential elasticity of multimodular megaenzymes.
#Interfacing mtty drake c line series#
We generate a series of precise domain-inactivating mutations in thalassospiramide assembly lines, and present evidence for an unprecedented biosynthetic model that invokes intermodule substrate activation and tailoring, module skipping and pass-back chain extension, whereby the ability to pass the growing chain back to a preceding module is flexible and substrate driven. Here, we report the heterologous reconstitution and comprehensive characterization of two hybrid NRPS–PKS assembly lines that defy many standard rules of assembly line biosynthesis to generate a large combinatorial library of cyclic lipodepsipeptide protease inhibitors called thalassospiramides. Modular nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) enzymatic assembly lines are large and dynamic protein machines that generally effect a linear sequence of catalytic cycles.
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