Microbial Synthesis of Antibiotic Precursor Kanosamine and Value-Added Chemical Shikimic Acid

摘要

Kanosamine is a naturally occurring antibiotic in several bacterial species including Bacillus and Amycolatopsis and the biosynthetic precursor of 3-amino-5-hydroxybenzoic acid, the building block for ansamycin family of antibiotics. It is also the nitrogen source in the aminoshikimate pathway. The kanosamine-synthesizing operon from Bacillus subtilis includes glucose-6-phosphate 3-dehydrogenase-encoding ntdC, 3-oxo-glucose-6-phosphate:glutamate aminotransferase- encoding ntdA, and kanosamine-6-phosphate phosphatase-encoding ntdB . Heterologous expression in E. coli SP1.1 strain produces approximately 8 g/L kanosamine in both glucose-rich and glucose-limited fed-batch fermenter conditions. This study confirms the proposed biosynthesis of kanosamine, in addition to providing a reproducible microbial synthesis for the antibiotic precursor.;Starch-based feedstocks, the primary choice of carbon source for commercial production of biobased fuels and chemicals, must be replaced by non-food-based feedstocks derived from agricultural biomass and residues to avoid competition between chemical uses and food uses of carbohydrates. To illustrate this concept, 1 g/L shikimic acid was produced in shake flask experiments of the strain E. coli SP1.1/pKD12.138 using anaerobic digestion hydrolysate containing glucose, xylose, and various compounds like furfural, 5-hydroxymethyl furfural, ferulic acid and coumaric acid as the carbon source. Model fed-batch fermentations with the same microbe using a 4% (w/v) glucose-xylose feed equivalent to the sugar concentrations in the AD hydrolysate resulted in the synthesis of 4 g/L shikimic acid and 6 g/L quinic acid.