This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
|Superclasses:||Biosynthesis → Secondary Metabolites Biosynthesis → Sugar Derivatives Biosynthesis → Kanosamine Biosynthesis|
Expected Taxonomic Range: Bacteria
Kanosamine (3-amino-3-deoxy-D-glucose) is an antibiotic produced as an end product by Bacillus cereus [Milner96] and other bacteria [Fusetani87, Dolak80]. UDP-α-D-kanosamine is a proposed intermediate in kanamycin A biosynthesis in Streptomyces kanamyceticus [Kharel04] (see kanamycin biosynthesis). Kanosamine and UDP-α-D-kanosamine are also proposed intermediates in the biosynthesis of 3-amino-5-hydroxybenzoate (AHBA) [Arakawa02] (see pathway 3-amino-5-hydroxybenzoate biosynthesis) which is a precursor of the ansamycin and mitomycin classes of antibiotics (in [Yu01]) (see pathway rifamycin B biosynthesis).
Early work using Bacillus pumilus (previously known as Bacillus aminoglucosidicus) provided experimental evidence for the biosynthesis of kanosamine via UDP-α-D-glucose, although the genes involved were not identified [Umezawa68]. Subsequent work using Amycolatopsis mediterranei provided further evidence for the UDP-α-D-glucose pathway (this pathway). It has also been proposed that the kab genes of Bacillus cereus are involved in kanosamine biosynthesis, although the pathway was not determined [Kevany09]. More recently, an alternate route for the biosynthesis of kanosamine has been described in Bacillus subtilis subtilis 168, in which kanosamine is derived from D-glucopyranose 6-phosphate rather than UDP-α-D-glucose [Vetter13] (see pathway kanosamine biosynthesis II).
About This Pathway
This is a proposed pathway for kanosamine biosynthesis in Amycolatopsis mediterranei [Guo02, Arakawa02]. Evidence suggests that kanosamine is the source of the nitrogen atom in the 3-amino-5-hydroxybenzoate biosynthetic pathway (aminoshikimate pathway) [Guo02, Arakawa02] as indicated in the pathway link. This is in contrast to the original proposal that the nitrogen atom was derived from transamination of D-erythrose 4-phosphate to 1-deoxy-1-imino-D-erythrose 4-phosphate by L-glutamine [Kim96g]. Preliminary studies using recombinant enzymes coexpressed in Escherichia coli suggested that the products of genes rifK and rifL may form a complex, jointly converting UDP-α-D-glucose to UDP-α-D-kanosamine through a UDP-3-dehydro-α-D-glucose intermediate (see comment listed as reference 25 in [Arakawa02]). These reactions produce NADH and use L-glutamine as a nitrogen source for kanosamine [Arakawa02]. The product of gene rifM has been predicted to encode a UDP-kanosamine phosphatase that catalyzes the conversion of UDP-α-D-kanosamine to kanosamine. This gene product and that of rifL have been shown to be essential for 3-amino-5-hydroxybenzoate biosynthesis [Yu01]. Reviewed in [Floss11].
Superpathways: superpathway of rifamycin B biosynthesis
Variants: kanosamine biosynthesis II
Relationship Links: KEGG:PART-OF:rn01051
Arakawa02: Arakawa K, Muller R, Mahmud T, Yu TW, Floss HG (2002). "Characterization of the early stage aminoshikimate pathway in the formation of 3-amino-5-hydroxybenzoic acid: the RifN protein specifically converts kanosamine into kanosamine 6-phosphate." J Am Chem Soc 124(36);10644-5. PMID: 12207505
Floss11: Floss HG, Yu TW, Arakawa K (2011). "The biosynthesis of 3-amino-5-hydroxybenzoic acid (AHBA), the precursor of mC7N units in ansamycin and mitomycin antibiotics: a review." J Antibiot (Tokyo) 64(1);35-44. PMID: 21081954
Fusetani87: Fusetani N, Ejima D, Matsunaga S, Hashimoto K, Itagaki K, Akagi Y, Taga N, Suzuki K (1987). "3-Amino-3-deoxy-D-glucose: an antibiotic produced by a deep-sea bacterium." Experientia 43(4);464-5. PMID: 3569498
Kharel04: Kharel MK, Subba B, Basnet DB, Woo JS, Lee HC, Liou K, Sohng JK (2004). "A gene cluster for biosynthesis of kanamycin from Streptomyces kanamyceticus: comparison with gentamicin biosynthetic gene cluster." Arch Biochem Biophys 429(2);204-14. PMID: 15313224
Kim96g: Kim C-G, Kirschning A, Bergon P, Zhou P, Su E, Sauerbrei B (1996). "Biosynthesis of 3-amino-5-hydroxybenzoic acid, the precursor of mC7N units in ansamycin antibiotics." J. Am. Chem. Soc. 118, 7486-7491.
Vetter13: Vetter ND, Langill DM, Anjum S, Boisvert-Martel J, Jagdhane RC, Omene E, Zheng H, van Straaten KE, Asiamah I, Krol ES, Sanders DA, Palmer DR (2013). "A Previously Unrecognized Kanosamine Biosynthesis Pathway in Bacillus subtilis." J Am Chem Soc 135(16);5970-3. PMID: 23586652
Yu01: Yu TW, Muller R, Muller M, Zhang X, Draeger G, Kim CG, Leistner E, Floss HG (2001). "Mutational analysis and reconstituted expression of the biosynthetic genes involved in the formation of 3-amino-5-hydroxybenzoic acid, the starter unit of rifamycin biosynthesis in amycolatopsis Mediterranei S699." J Biol Chem 276(16);12546-55. PMID: 11278540
August98: August PR, Tang L, Yoon YJ, Ning S, Muller R, Yu TW, Taylor M, Hoffmann D, Kim CG, Zhang X, Hutchinson CR, Floss HG (1998). "Biosynthesis of the ansamycin antibiotic rifamycin: deductions from the molecular analysis of the rif biosynthetic gene cluster of Amycolatopsis mediterranei S699." Chem Biol 5(2);69-79. PMID: 9512878
Kim98: Kim CG, Yu TW, Fryhle CB, Handa S, Floss HG (1998). "3-Amino-5-hydroxybenzoic acid synthase, the terminal enzyme in the formation of the precursor of mC7N units in rifamycin and related antibiotics." J Biol Chem 273(11);6030-40. PMID: 9497318
Schupp98: Schupp T, Toupet C, Engel N, Goff S (1998). "Cloning and sequence analysis of the putative rifamycin polyketide synthase gene cluster from Amycolatopsis mediterranei." FEMS Microbiol Lett 159(2);201-7. PMID: 9503613
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