Laboratory of Microbial Natural Products
(PI: Dr. Yongsheng Che)
Introduction
1. Research Interests

Ecology-based investigations of fungal secondary metabolites as potential
sources of new antibacterial, antifungal and antiinsectan natural products.

High Throughput screening of microbial metabolites against various
medically important targets for potential therapeutics.

Discovery of potential taste modifiers from natural sources.
2. Principal Investigator:
Professor Yongsheng Che
09/85-07/89, BS, Polymer Science, Nankai University
01/94-06/95, MS, Organic Chemistry, Clarkson University
08/95-03/00, Ph.D., Organic Chemistry (Natural Products), University of Iowa
03/00-03/01, Research Scientist, OSI Pharmaceuticals, Inc.
03/01-08/02, Senior Research Scientist, OSI Pharmaceuticals, Inc.
08/02-01/05, Senior Research Scientist, Givaudan Roure
02.05-present, Professor, Institute of Microbiology, Chinese Academy of Sciences
4. Group members
Erwei Li, Ph.D. Research Scientist
Hejiao Hu, MS, Research Assistant
Fengxia Li, BS, Research Assistant/Secretary
Xianwei Zhou, Ph.D. student
Ling Liu, Ph.D. student
Huijuan Guo, MS student
Yan Li, MS student
Ji Luo, MS student
Background and Significance
Natural products are important sources for new medicines, and numerous
bioactive natural products have been discovered from plants, microorganisms, and
marine sources. According to a recent review, of the 1031 New Chemical Entities
(NCEs) to reach the market as drugs covering all diseases during the period of
1981-2002, roughly 60% are either natural products, natural product-derived, natural
product mimics, or biologicals (peptides or proteins) of natural origin.
This is
especially evident in the fields of cancer and infectious diseases, where over 60% and
75% of the drugs are of natural origin, respectively.
Notable examples from fungal
sources are multi-billion dollar classes of antibiotics that include penicillins and
cephalosporins, the important and widely used cholesterol-lowing agents lovastatin,
compactin, and pravastatin, and the immunosuppresant cyclosporin A.
Ecology-based approaches have proven to be extremely valuable in the search for
bioactive natural products.
It is generally accepted that plants produce compounds
that serve as chemical defenses against insects, herbivorous vertebrates, or microbial
attack. Certain marine animals are also known to produce or accumulate
antifeedant/ichthyotoxic agents that protect them from attack by predators.
Similar
interactions occur among fungi, and can also serve as leads to the discovery of new
bioactive metabolites.
For example, observed avoidance of the sclerotia of
Aspergillus flavus by the ecologically relevant insect Carpophilous hemipterus led to
the discovery of a variety of new antiinsectan natural products.
Chemical studies of
mycoparasites (fungicolous fungi that are parasitizes of other fungal species) could be
viewed as a logical approach to the search for new antifungal agents.
For example,
fungi that attack the sclerotia of A. flavus have been found to produce new secondary
metabolites with activity against A. flavus. These and other examples clearly
demonstrate the utility of applying ecology-based approach in natural products
research.
Major Achievements
Representative publications
Pseudodestruxins A and B:
New Cyclic Depsipeptides from the Coprophilous
Fungus Nigrosabulum globosum, Y. Che, D. C. Swenson, J. B. Gloer, B. Koster, D.
Malloch.
J. Nat. Prod. 2001, 64, 555-558.
Phomadecalins A-D and Phomapentanone A: New Bioactive Metabolites from
Phoma sp. NRRL 25697, a Fungal Colonist of Hypoxylon Stromata, Y. Che, J. B.
Gloer, D. T. Wicklow.
J. Nat. Prod. 2002, 65, 399-402.
Decipienin A and Decipienolides A-B:
New Bioactive Metabolites from the
Coprophilous Fungus Podopsora decipiens, Y. Che, J. B. Gloer, B. Koster, D.
Malloch.
J. Nat. Prod. 2002, 65, 916-919.
Communiols A-D: New Mono- and Bis-Tetrahydrofuran Derivatives from the
Coprophilous Fungus Podospora communis, Y. Che, J. B. Gloer, J. A. Scott, D.
Malloch.
Tetrahedron Lett. 2004, 45, 6891-6894.
Curvicollides A-C:
New Polyketide-Derived Lactones from a
Sclerotium-Colonizing Isolate of Podospora curvicolla (NRRL 25778), Y. Che, J. B.
Gloer, D. T. Wicklow.
Org. Lett. 2004, 6, 1249-1252.
Communiols E-H: New Bioactive Secondary Metabolites from the Coprophilous Fungus
Podospora communis, Y. Che, J. B. Gloer, J. A. Scott, D. Malloch.
J. Nat. Prod. 2005, 68,
435-438.
Future Research Plan
Overwhelming evidence indicates that bioactive secondary metabolites function as
chemical defenses, naturally selected to bind to specific pharmacological receptors.
Bioassay-guided screening of previously uninvestigated microorganisms, and those
that occupy specific, chemically defended ecological niches will result in the
discovery of new chemo types with unique biological properties.

In the immediate future，the goal is to focus on the discovery of novel natural
products from unique biological sources using cell-based and mechanism-based
bioassays, with an effort toward studying the interactions of these compounds
with pharmacologically important receptors.

Utilizing microbial resources and High Throughput Screening platform at the
Institute of Microbiology, the natural products group will conduct detailed
chemical investigations on those active hits obtained from screening of microbial
metabolite library against medically important targets, including infectious
diseases, metabolic diseases, and cancer.

Emphasis will be also placed upon discovery of novel taste modifiers from
natural sources, such as selected fungi and plants by employing various
techniques in the natural products research.
The initial goal is to discover novel
natural products with sweetness enhancing property and umami effect.
The ultimate goal to is discover novel natural products that can be used for
potential therapeutics and natural taste modifiers.