Summary of my work
Together with my collaborators, I have developed efficient gene finding systems from organisms that producing important antibiotics including those in the polyene, polyether and aminoglycoside classes with medical, agricultural and veterinary applications. The established systems enabled us to identify biosynthesis pathways of the antibiotics. The information obtained is used for production of antibiotics and novel compounds by metabolic engineering or combinatorial biosynthesis, and may potentially be used for engineering plants against fungal/insect attacks. These studies were initiated to exploit the genetic resources in China. A major subject of this important field is genetics of the biosynthesis of antifungal antibiotics in the bacteria Streptomyces. There is an urgent need to increase the production and to discover new antifungal compounds for applications in agriculture and medicine. We have been successful in making use of known unique microbial resources in China. We made a great effort to develop Streptomyces strains that produce important antifungal compounds. Our original research with international collaborations in gene identifications and genetic manipulations led to the improved production of existing drugs and compounds with desired specific activities as industrial materials or novel drug candidates.
We also worked extensively on DNA modification in bacteria. Our studies led to the finding of a new type of DNA modification mechanism, by which the DNA backbone is modified by sulfur to form phosphorothioate. Our discovery of this new DNA modification mechanism received high recognitions in the field, and was listed as one of the Top 10 Scientific Technological Achievements from Chinese Universities in the Year 2005 and one of the Top 10 Globe Science News in 2007. Our studies on the DNA modification mechanism by sulfur have been over a decade and were partly conducted at Cornell during my visit at Cornell University.
Impacts in China
Our work on validamycin A is especially worth mentioning. Validamycin A is the most successful agricultural antibiotics in China, and has been used for many years as an environmental-friendly drug. No emergence of drug resistance in the field has been reported, and both protective and control effects are dramatic. It is widely used, especially in Asia, to control sheath blight disease of rice and the damping-off of cucumber seedlings caused by the fungus Pellicularia sasakii (Rhizoctonia solani). Validamycin A also possesses insecticidal properties. The production of validamycin in China accounts for at least 7 tons each year, with a coverage of at least 15% of rice production areas, earning at least 500,000,000 Chinese yuan each year. With the sequencing and functional analysis of the DNA from the bacterium Streptomyces hygroscopicus 5008, we successfully reconstituted the biosynthetic pathway of validamycin A for production of the antibiotics. Now the essential genes are available for engineering rice and other vulnerable crops to protect the plants against the sheath blight fungus (Pellicularia sasakii) and insects. The work also helped efficient production of several drug precursors. Of course, this work aroused great interest from validamycin-producing companies in China, and has immediately increased their production capacity.
Our research achievement on validamycin was also highlighted by “Nature Biotechnology” in 2006, and was named as one of the Top 10 Scientific & Technological Achievements from Chinese Universities in the Year 2006 by the Chinese Ministry of Education, and also was part of the Grade II Award in the category of China National Natural Science.
Other examples of successful efforts along this line included identification of biosynthetic pathoway genes for various antibiotic compounds that are useful for control of pests and diseases in plants and humans.
- 2004, Grade I prize winner for Science & Technology Progress, Shanghai Municipal Government.
- 2005, Leading Figure for Science & Technology, by Shanghai Commission of Science & Technology.
- 2005, “One of the ten talents in Scientific & Technological invention,” by Shanghai.
- 2005, “2005 Top 10 Chinese University Achievements named by the Ministry of Education, China,” for “A novel DNA modification by sulfur.”
- 2006, “2006 Top 10 Chinese University Achievements named by the Ministry of Education, China,” for “Reconstituted validamycin and its derivatives.”
- 2007, Model Worker, named by Shanghai Municipal Government.
- 2007, Grade I prize for Natural Science, Ministry of Education, China.
- 2008, Model Worker, named by Central Chinese Government.
- 2008, Grade II prize for National Natural Science, Ministry of S&T, China.
- 2005, Election into the Chinese Academy of Sciences.
- 2006, Election into the Academy of Sciences for the Developing World (formally the Third World Academy of Sciences, TWAS).
- 2010, Election into the American Academy of Microbiology.
For details on publications and projects see the scholar's website.