Biosynthesis of Gabosines A, B, and C, Carba Sugars fromStreptomyces cellulosae

Abstract

The biosynthesis of the gabosines A−C (3−5) was studied by feeding cultures of Streptomyces cellulosae subsp. griseorubiginosus (strain S 1096) with 13C‐labeled precursors. Although the carba sugars are structurally related to shikimic acid, the biosynthetic origin was found to be different to the shikimate pathway. The results revealed that the gabosines are formed via a pentose phosphate pathway by cyclization of a heptulose phosphate intermediate. This intermediate arises from a triose phosphate by successive transfer of two C2 fragments by transketolases. This pathway is identical as that described for valienamine (7), the aminocarba sugar moiety of validamycin, and acarbose (2). The results from biosynthetic studies are discussed on the background of the variety of gabosines found in nature.

The biosynthesis of acarbose and validamycin

“…2). A similar origin has recently been demonstrated by Zeeck and coworkers for the gabosines A, B, and C from Streptomyces cellulosae 37…”

Big Effects from Small Changes: Possible Ways to Explore Nature's Chemical Diversity

“…Compared to this strain with its mainly reduced type I polyketides, S. cellulosae ssp. griseorubiginosus (strain S 1013) produces only four compounds but originated from three different biogenetic pools (Scheme ) 10–13. The gabosines D ( 17 ) and E ( 18 ) are derived from intermediates of the sugar pathway, hexacyclinic acid ( 19 ) represents one of the rare polycyclic type I polyketides, and compound 20 is an angustmycin A derivative 14.…”

A Comparative Analysis of the Sugar Phosphate Cyclase Superfamily Involved in Primary and Secondary Metabolism

“…The biosynthesis of a diverse array of clinically relevant natural products involves pathways that parallel the initial steps in shikimate biosynthesis (the primary route to aromatic amino acids) 1. These classes of natural products include the ansamycin antibiotics, such as rifamycin,2, 3 ansamitocin,4 and geldanamycin;5 the aminoglycoside antibiotics, such as neomycin,6 kanamycin,7 butirosin,8 and gentamicin;9, 10 and the C 7 ‐cyclitol‐containing compounds, such as acarbose,11, 12 the validamycins,13, 14 the gabosines,15 and the pyralomicins16 (Scheme 1).…”