Liangcheng Du
Associate Professor
Hamilton Hall 729
402.472.2998
ldu@unlserve.unl.edu
Du Research Group
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Recent Publications
Current Research
Biosynthetic mechanism for fungal polyketides – Many important polyketide natural products are produced by filamentous fungi, such as the mycotoxin fumonisins produced by Fusarium verticillioides (Figure 1) and the cholesterol-lowering drug lovastatin (MervacorTM) by Aspergillus terreus. We are using genetic and biochemical approaches to understand the mechanism by which the fungi synthesize these complex metabolites. The biosynthetic genes have been specifically knocked out and functionally complemented to define the role of the genes. The fungal genes also have been introduced into heterologous hosts, such as E. coli and baker's yeast, to produce the corresponding enzymes. The activity of these enzymes is subsequently defined in vitro to obtain the direct evidence for the function of the biosynthetic genes.
Genetics and function of novel antibiotics – In this collaborative project, we are studying the genetics and function of a novel antifungal metabolite, HSAF, isolated from the biocontrol agent Lysobacter enzymogenes C3. MS and NMR data suggest that HSAF has a chemical structure that is distinct from any of the known fungicides or antifungal drugs. Genetic analysis of a model fungus has showed that HSAF targets the biosynthesis of a specific group of sphingolipids that are required for polarized hyphal growth (Figure 2). HSAF represents a promising candidate for new fungicides and antifungal drugs with new chemistry and an unprecedented mode of action. A DNA fragment has been sequenced and four genes, including a polyketide synthase gene (PKS), have been identified. The PKS gene has been knocked out, and the resulted mutants lost the ability to produce HSAF and to inhibit fungal growth (Figure 2). The results demonstrate the polyketide origin of HSAF biosynthesis. The biosynthetic genes provide the basis for genetic engineering to produce new fungicides and antifungal drugs.
- Biosynthesis
- Metabolic engineering
- Natural products
- Polyketides
- Nonribosomal peptides
- Mycotoxins
- Fungicides
- Bio-control
- Antibiotics
- Gene cloning/expression
- Redox enzymes
A graduate or postdoctoral student in my group can expect to receive training at the interface of chemistry and biology, including clone biosynthetic genes, express genes in heterologous hosts, purify enzymes and characterize activities, mutagenesis and recombination, metabolic engineering, fermentation, and isolation and structural determination of metabolites.
