Tylosin biosynthesis

Kreuzman AJ, Turner JR, Yeh WK (1988) Two distinctive O-methyltransferases catalyzing penultimate and terminal reactions of macrolide antibiotic (tylosin) biosynthesis. Substrate specificity, enzyme inhibition, and kinetic mechanism. J Biol Chem 263 15626-15633... 

Butler AR, Bate N, Cundliffe E (1999) Impact of thioesterase activity on tylosin biosynthesis in Streptomyces fradiae. Chem Biol 6 287-292... 

Baltz RH. Seno ET. Genetics of Streptomyces fraSae and tylosin biosynthesis. Annu Rev Mkiobioi 1988 42=547-574. 

Cox KL, Fishman SE, Larson JL, Staruak R. Reynolds PA, Yeh WK, Van Frank RM, Birmingham VA. Hershberger CL, Seno ET. The use of recombinant DNA techniques to study tylosin biosynthesis and resistance in Streptomyces/rodwe. J Nat Prod 1986 49 971-980. 

A pathway has been suggested for the latter stages of tylosin biosynthesis, which includes attachment of three glycosidically bound sugars, mycinose, mycaminose and mycarose, to a 16-membered... 

The first two enzymatic steps are common to the biosynthesis of all 6DOHs and lead to the biosynthesis of the intermediate TDP-4-keto-6-deoxy-D-glucose. These enzymatic reactions have been extensively studied in different sugar biosynthesis pathways, such as tylosin or mithramycin [13]. 

Antibiotics that block bacterial protein biosynthesis. Macrolides Target the 508 ribosome subunit. Tylosin, which is widely used in the livestock Clarithromycin (biaxin) Semisynthetic and has better intracellular penetration compared to earlier... 

Seno ET, Hutchinson CR (1986) The biosynthesis of tylosin and erythromycin Model systems for the studies of the genetics and biochemistry of antibiotic formation. In Queener SW, Day LE (eds) The Bacteria Volume IX Antibiotic-Producing Streptomyces. Academic Press, Orlando, p 231... 

It may be argued that this unusual biosynthetic sequence is due to the unique composition and organization of the dps (dauno- or doxorubicin polyketide synthase) genes of Streptomyces peucetius [88]. But, also in more typical biosyntheses of polyketide oligodeoxysaccharides, for example, the macrolides erythromycin A (14) [24, 58, 89] in Saccharopolyspora erythraea and tylosin in Streptomyces fradiae [90], or urdamycin biosynthesis in Streptomyces fradiae TU2717 [77,91,... 

From these examples it is clear that nature also provides convergent alternatives to the linear assembly of deoxysaccharides, as was, for example, observed in tylosin [90] or streptomycin (24) biosynthesis [72], A linear strategy is certainly also true for other aminoglycosides, although in the case of neomycin biosynthesis, an alternative disaccharyl transfer has been discussed [70],... 

Tylosin 33 from Streptomyces fradiae is a representative member of the large family of 16-membered macrolide antibiotics commonly utilised in veterinary medicine. The aglycone core, tylactone 34 is constructed from two acetate, five propionate and one butyrate units [68, 69]. The processive mechanism for its biosynthesis was demonstrated by the pioneering contributions of Hutchinson... 

Tylosin [46-49] (Fig. 6), produced by Streptomyces fradiae, was one of the first antibiotics for which a comprehensive set of blocked mutants was isolated. They were used to help define the biosynthetic pathway. Whereas erythromycin is a 14-membered macrolide, tylosin has a 16-membered lactone structure. The gene for the final step of biosynthesis was cloned by reverse genetics from the protein sequence of the enzyme [46], and specific segments of surrounding DNA were found to complement other classes of blocked mutants. The formation of tylosin aglycon, protylonolide, is involved in five polyketide synthases. 

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