Delineation of gilvocarcin, jadomycin, and landomycin pathways through combinatorial biosynthetic enzymology

Eight-Membered Ring-Containing Jadomycins: Implications for Non-enzymatic Natural Products Biosynthesis

“…11 In the jadomycin cluster, JadG has been identified as the enzyme responsible for the B ring opening. 9,12 The C−C cleavage proceeds via a Baeyer− Villiger oxidation producing an oxepinone intermediate. 13 The resulting reactive aldehyde couples in a non-enzymatic fashion to a singular amino acid in the culture medium, forming an imine intermediate that cyclizes into the jadomycin backbone (Scheme 1).…”

Characterization of l-Digitoxosyl-phenanthroviridin from Streptomyces venezuelae ISP5230

“…HMBC and 2D-NOESY correlations from H5 to C4 and H4, respectively, confirmed the proximity of the proton to the A-ring; HMBC analysis also identified a correlation to the C6a position of the B-ring. 1 …”

“…4,5 Interestingly, amino acid incorporation has been shown to proceed through a spontaneous process in which the enzyme JadG is responsible for a C−C bond cleavage at the B-ring (Scheme 1). 1,6,7 This proceeds via a Baeyer−Villiger-type mechanism producing a reactive aldehyde intermediate, which couples with an amino acid, forming an imine, which undergoes spontaneous cyclization and oxidation to produce a five-membered oxazolone ring (Scheme 1). This mechanism has been confirmed through both extensive biosynthetic and total synthetic studies, 7−9 and exploitation of this mechanism by precursor-directed derivatization with varying amino acids has led to the isolation of upward of 25 jadomycin analogues.…”

“…1 The structural diversity of this large family of natural products arises from the configurations of polyaromatic angucycline backbones and the modification of these scaffolds by a wide array of post-PKS tailoring enzymes. A great deal of interest in their continued isolation and characterization is in anticipation of identifying novel bioactive natural products.…”

The International Conference of Natural Product Biosynthesis (ICNPB, 8th US–Japan seminar on the Biosynthesis of Natural Products)

“…In this study, glycosylation, dehydration and oxidation catalyzed by enzymes of the gilvocarcin and jadomycin biosynthetic pathways were characterized. 11 FUNGAL PKS AND EXPRESSION Session 3 (Fungal PKS and expression) opened with a lecture by Professor Isao Fujii (Iwate Medical University), who reported the biosynthetic study of a type III PKS from A. oryzae, which produces csypyrone B1. [1,2-13 C 2 ]Acetate feeding experiments showed that csypyrone B1 could be derived from succinyl-CoA and malonylCoAs.…”