Sungeidines from a Non-canonical Enediyne Biosynthetic Pathway

Abstract

We report the genome-guided discovery of sungeidines, a class of microbial secondary metabolites with unique structural features. Despite evolutionary relationships with dynemicin-type enediynes, the sungeidines are produced by a biosynthetic gene cluster (BGC) that exhibits distinct differences from known enediyne BGCs. Our studies suggest that the sungeidines are assembled from two octaketide chains that are processed differently than those of the dynemicin-type enediynes. The biosynthesis also involves a unique activating sulfotransferase that promotes a dehydration reaction. The loss of genes, including a putative epoxidase gene, is likely to be the main cause of the divergence of the sungeidine pathway from other canonical enediyne pathways. The findings disclose the surprising evolvability of enediyne pathways and set the stage for characterizing the intriguing enzymatic steps in sungeidine biosynthesis.

Anthraquinone-fused enediynes: discovery, biosynthesis and development

“…The structure of compound A was established by X-ray crystallography as 15-deoxy DYN A (8). 12 In addition to compound 1, a few DYN A congeners, namely DYN L (9), M (10) and N (11), 38 and O (12), P (13) and Q (14), 39 were also isolated from the fermentation broth of M. chersina. Treatment of DYN A with methyl thioglycolate generated DYN H (15) and DYN S (16).…”

“…MD118. 10 Although the sungeidines were not isolated in the enediyne form, the comparison of their BGC with other known BGCs for AFEs suggested that the sungeidine pathway is closely related to the other AFE pathways. 11 The structures of the representative enediynes and the AFEs, i.e., DYN A (1), UCM (2), TNM A (3), YPM A (4), sealutomicin A (5) and sungeidine A (6) are shown in Fig.…”

“…22 However, due to the lack of sufficient information on the BGCs and the biosynthetic intermediates, no signicant progress was made in the rst two and a half decades since the discovery of the rst AFE. In the past ve years, comparative studies of the BGCs 7,8,10 and the accumulated biosynthetic intermediates of AFEs have provided precious opportunities to disclose the biosynthesis of the anthraquinone moieties, 23,24 the coupling of the anthraquinones with the enediyne core, 10,25 and the late-stage tailoring steps. [26][27][28] The total synthesis of DYN A was actively pursued in the early 1990s.…”

Future trends in synthetic biology in Asia

“…A Chinese group applied comparative genomic and transcriptomic analyses to the resurrection efforts of the plant Selaginella tamariscina and revealed genetic mechanisms of drought tolerance in plants 65 . Similar multi‐omics approaches also led to the discovery of novel biosynthetic pathways from microbes isolated from Singapore's native environment, 66,67 as well as silent secondary metabolites in Streptomyces species 68 . Such novel discoveries not only add to our understanding of the biological systems, but also enrich the available molecular tools for synthetic biology research and applications.…”

Yield improvement of enediyne yangpumicins in Micromonospora yangpuensis through ribosome engineering and fermentation optimization

“…[1,2] Many valuable compounds have been isolated from Micromonospora in diverse environmental niches, such as turbinmicin, diazepinomicin, diazaquinomicin, and sungeidine. [3][4][5][6] In addition, several clinical used drugs, including gentamicin (antibiotic) and calicheamicin (anticancer), are also produced by Micromonospora species. [7] The recent analysis of biosynthetic gene clusters (BGCs) of Micromonospora isolates further revealed that they have great potential to produce novel natural products.…”