A5025915538- Microbial Natural Products and Biosynthesis
- Photosynthetic Processes and Mechanisms
- Plant biochemistry and biosynthesis
- Enzyme Catalysis and Immobilization
- Enzyme Structure and Function
- Amino Acid Enzymes and Metabolism
- Click Chemistry and Applications
- Chemical Synthesis and Analysis
- Chemical synthesis and alkaloids
- Tuberculosis Research and Epidemiology
- RNA and protein synthesis mechanisms
- Phytochemistry and Bioactivity Studies
- biodegradable polymer synthesis and properties
- Microbial Community Ecology and Physiology
- Mycobacterium research and diagnosis
- Electrospun Nanofibers in Biomedical Applications
- Bone Tissue Engineering Materials
- Genomics and Phylogenetic Studies
- Microbial Metabolic Engineering and Bioproduction
- Marine Sponges and Natural Products
- Biochemical and Molecular Research
University of California, Berkeley
2017-2021
Significance Mycobacterium tuberculosis is the leading causative agent of tuberculosis, from which millions die annually. A putative lipopeptide biosynthetic gene cluster has been shown to be essential for survival this pathogen in hosts, and homologous clusters have also found all pathogenic mycobacteria other species Actinobacteria. We identified function these making a family isonitrile lipopeptides. The biosynthesis several unique features, including an unprecedented mechanism synthesis....
P. putida lysine metabolism can produce multiple commodity chemicals, conferring great biotechnological value. Despite much research, the connection of catabolism to central in remained undefined. Here, we used random barcode transposon sequencing fill gaps . We describe a route 2-oxoadipate (2OA) catabolism, which utilizes DUF1338-containing protein 5260 (PP_5260) bacteria. its prevalence many domains life, proteins have had no known biochemical function. demonstrate that PP_5260 is...
In this study, an unsaturated copolyester, poly[(R)-3-hydroxybutyrate-co-(R)-3-hydroxy-10-undecenoate] (PHBU), was produced by engineered strain of Escherichia coli, cross-linked via thiol-ene click chemistry, and analyzed for improved physical properties biocompatibility with human mesenchymal stem cells. By cross-linking the PHBU polymer, increase in tensile strength greater than 200% to 26.2 MPa observed, resulting a material closer those relevant soft tissue replacement. Results showed...
Triacsins are a family of natural products having in common an N-hydroxytriazene moiety not found any other known secondary metabolites. Though many studies have examined the biological activity triacsins lipid metabolism, their biosynthesis has remained unknown. Here we report identification triacsin biosynthetic gene cluster Streptomyces aureofaciens ATCC 31442. Bioinformatic analysis led to discovery tacrolimus producer tsukubaensis NRRL 18488 as new producer. In addition targeted...
A facile method for the quick discovery and quantification of isonitrile compounds from microbial cultures was established based on isonitrile–tetrazine click reaction. This successfully applied to rediscovery diisonitrile antibotic SF2768 an unknown strain Streptomyces tsukubensis. Finally, in situ reduction further enabled bioorthogonal ligation primary secondary isonitriles first time.
Abstract Microbial biosynthetic gene clusters are a valuable source of bioactive molecules. However, because they typically represent small fraction genomic material in most metagenomic samples, it remains challenging to deeply sequence them. We present an approach isolate and samples using microfluidic automated plasmid library enrichment. Our provides deep coverage the target cluster, facilitating reassembly. demonstrate by isolating sequencing type I polyketide synthase from Antarctic...
Abstract Despite intensive study for 50 years, the biochemical and genetic links between lysine metabolism central in Pseudomonas putida remain unresolved. To establish these links, we leveraged Random Barcode Transposon Sequencing (RB-TnSeq), a genome-wide assay measuring fitness of thousands genes parallel, to identify multiple novel enzymes both L- D-lysine metabolism. We first describe three pathway that catabolize L-2-aminoadipate (L-2AA) 2-ketoglutarate (2KG), connecting TCA cycle. One...
A facile method for the quick discovery and quantification of isonitrile compounds from microbial cultures was established based on isonitrile-tetrazine click reaction. in situ reduction further enabled bioorthogonal ligation primary secondary isonitriles first time.
Abstract A putative lipopeptide biosynthetic gene cluster is conserved in many species of Actinobacteria , including Mycobacterium tuberculosis and M. marinum but the specific function encoding proteins has been elusive. Using both vivo heterologous reconstitution intro biochemical analyses, we have revealed that five enzymes are capable synthesizing a new family isonitrile lipopeptides (INLPs) through thio-template mechanism. The biosynthesis features generation from single precursor Gly...
Abstract Triacsins are a family of natural products containing an N-hydroxytriazene moiety not found in any other known secondary metabolites. Though many studies have examined the biological activity triacsins lipid metabolism, biosynthesis has remained unknown. Here, we report identification triacsin biosynthetic gene cluster Streptomyces aureofaciens ATCC 31442. Bioinformatic analysis led to discovery tacrolimus producer tsukubaensis NRRL 18488 as new producer. In addition targeted...
Abstract Triacsins are an intriguing class of specialized metabolites possessing a conserved N -hydroxytriazene moiety not found in any other known natural products. notable as potent acyl-CoA synthetase inhibitors lipid metabolism, yet their biosynthesis has remained elusive. Through extensive mutagenesis and biochemical studies, we here report all enzymes required to construct install the pharmacophore triacsins. Two distinct ATP-dependent were revealed catalyze two consecutive N-N bond...