The research interests of my group lie at the interface of chemistry and biology. We focus on generating complex biologically active compounds, such as polyketides, non-ribosomal peptides and complex sugars. To make these molecules, we use two complementary, very different methods, synthetic chemistry and metabolic engineering, which are unified by their reliance on a deep understanding of the biosynthetic origin of the target molecule.

Biosynthetic pathways often take advantage of intrinsically favorable reaction pathways in the formation of complex molecules. We identify these putative pathways and use their favorable, spontaneous chemistry as key elements in our total synthesis efforts. This provides us with rapid and elegant synthetic routes and allows us to test experimentally our proposed biosyntheses. We are currently involved in the biomimetic total syntheses of two complex polyketides, laulimalide and spiculoic acid.

Fermentation has many advantages over chemical synthesis in the production of large quantities of complex molecules, including scalability, cost and environmental impact. Unfortunately, many desired compounds are not currently available through fermentation. Using know biosynthetic enzymes, we are engineering lab friendly bacteria to produce new complex molecules. Our current focus is on developing an E. coli system for the overproduction of sialic acid and a Myxococcus xanthus system for the overproduction of polyketides.

Engineered biosynthetic pathways cannot yet be constructed to generate any desired complex molecule. In polyketide biosynthesis there are still many structural elements who's biosynthetic origins remain a mystery. By identifying and biochemically characterizing the enzymes or catalytic domains responsible for formation of these structural elements, we lay the foundation for their future incorporation into engineered biosynthetic pathways. We are currently working on characterizing thioesterase domains responsible for formation of macrodiolides and the catalytic domains responsible for tetrahydropyran formation.

Collaborators:
Dr Anthony G. Garza - (Univ. of Syracuse) Biofilm formation; bacterial development; stress resistance in bacteria

Dr. Robert Doyle - (Univ. of Syracuse) Bioinorganic, materials, medicinal inorganic

Dr. Roy Welch Lab - (Univ. of Syracuse) Molecular aspects of signaling among a homogeneous population of bacteria. Myxococcus xanthus and fruiting body development.

Process Science Inc. - Syracuse, NY - Development of halomicin antibiotic for third world countries

Dr. Clay C. C. Wang - (University of Southern California)

Dr. Yi Tang - (UCLA)

Dr. Christopher T. Walsh - (Harvard Med)

Dr. John Offer - (Oxford Glycobiology Institute)