Antibiotic biosynthesis: from natural to unnatural compounds.
The evolution of the field of biosynthesis from the unravelling of the mode of formation of natural products to the use of such knowledge to create new compounds is reviewed using examples from the author's laboratory. The discussion focuses on the mode of operation of type II (spore pigment PKS) and type I (rifamycin PKS) polyketide synthases and their diversion to generate unnatural products, and on the genetics and biochemistry of deoxysugar formation in granaticin biosynthesis as a prerequisite to combinatorial enzymatic synthesis of unusual glycosides.
Floss
H G
HG
Department of Chemistry, University of Washington, Seattle 98195-1700, USA.
D000192:Actinomycetales / Q000235:genetics / Q000378:metabolism*; D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000737:chemistry; D001688:Biological Products / Q000096:biosynthesis; D020650:Combinatorial Chemistry Techniques; D005818:Genetic Engineering / Q000379:methods; D009097:Multienzyme Complexes / Q000235:genetics* / Q000378:metabolism; D009285:Naphthoquinones / Q000737:chemistry / Q000378:metabolism*; D012294:Rifamycins / Q000096:biosynthesis* / Q000737:chemistry; D000095622:Benzoisochromanequinones
D000900:Anti-Bacterial Agents; D001688:Biological Products; D009097:Multienzyme Complexes; D009285:Naphthoquinones; D012294:Rifamycins; C033974:rifamycin B; C009811:granaticin; D000095622:Benzoisochromanequinones