A5046103895- Microbial Natural Products and Biosynthesis
- Plant biochemistry and biosynthesis
- Fungal Biology and Applications
- Biochemical and Structural Characterization
- Microbial Metabolism and Applications
- Peptidase Inhibition and Analysis
- Fungal and yeast genetics research
- Chemical synthesis and alkaloids
- Fermentation and Sensory Analysis
- Biochemical and Molecular Research
- Crystallization and Solubility Studies
- Alkaloids: synthesis and pharmacology
- X-ray Diffraction in Crystallography
- Microbial Metabolic Engineering and Bioproduction
University of California, Los Angeles
2018-2023
Biosynthetic pathways containing multiple core enzymes have potential to produce structurally complex natural products. Here we mined a fungal gene cluster that contains two predicted terpene cyclases (TCs) and nonribosomal peptide synthetase (NRPS). We showed the flv pathway produces flavunoidine 1, an alkaloidal terpenoid. The of 1 is tetracyclic, cage-like, oxygenated sesquiterpene connected dimethylcadaverine via C–N bond acylated with 5,5-dimethyl-l-pipecolate. roles all are established...
Significance A polyketide synthase and nonribosomal peptide synthetase hybrid gene cluster from the genome of Penicillium thymicola was identified through mining. Heterologous expression this leads to production pyranonigrin A. series experiments established that only four genes are sufficient biosynthesize Based on results current study, a biosynthetic pathway is proposed. © 2018 American Institute Chemical Engineers AIChE J , 64: 4182–4186,
Monoterpene indole alkaloids (MIAs) are a class of natural products comprised thousands structurally unique bioactive compounds with significant therapeutic values. Due to difficulties associated isolation from native plant species and organic synthesis these complex molecules, microbial production MIAs using engineered hosts highly desired. In this work, we report the engineering fully integrated Saccharomyces cerevisiae strains that allow de novo access strictosidine, universal precursor...
The fungal species Aspergillus flavus produces an alkaloid terpenoid, flavunoidine, through a hybrid biosynthetic pathway combining both terpene cyclase and nonribosomal peptide synthetase enzymes. Flavunoidine consists of tetracyclic, oxygenated sesquiterpene core decorated with dimethyl cadaverine 5,5-dimethyl-l-pipecolate moieties. Unique to the flavunoidine is FlvF, putative enzyme implicated in stereospecific C-N bond formation as linked generate pre-flavunoidine. Here, we report 2.6 Å...
Genome mining of biosynthetic pathways with no identifiable core enzymes can lead to discovery the so-called unknown (biosynthetic route)-unknown (molecular structure) natural products. In this work, we focused on a conserved fungal pathway (ank) that lacks canonical enzyme, and used heterologous expression identify associate product be highly modified cyclo-arginine-tyrosine dipeptide (cRY). Biochemical characterization ank led identification new arginine-containing cyclodipeptide synthase...
Natural products generated by biosynthetic enzymes provide complex structural diversity. Several fungal species have evolved to obtain this diversity combining several core in a pathway, including polyketide synthases (PKS), nonribosonal peptides (NRPS), and terpene cyclases (TC) along with accessorizing such as transferases oxidoreductases. Combinations of different hybrid gene clusters affords structurally scaffolds unachievable single enzyme. Recently, the Tang laboratory characterized...