Discovery of Tetronate-Containing Kongjuemycins from a Coral-Associated Actinomycete and Elucidation of Their Biosynthetic Origin DOI
Zhuangjie Fang, Qingbo Zhang, Weiliang Xiong

et al.

Organic Letters, Journal Year: 2023, Volume and Issue: 25(34), P. 6346 - 6351

Published: Aug. 22, 2023

Tetronate antibiotics make up a growing family of natural products with wide variety biological activities. Herein, we report four new tetronates kongjuemycins (KJMs, 5-8) from coral-associated actinomycete Pseudonocardia kongjuensis SCSIO 11457, and the identification characterization KJM biosynthetic gene cluster (kjm) by heterologous expression, comparative genomic analysis, isotope labeling, knockout studies. The biosynthesis KJMs is demonstrated to harness diverse precursors primary metabolism for building secondary metabolites.

Language: Английский

The shikimate pathway: gateway to metabolic diversity DOI
Vikram V. Shende, Katherine D. Bauman, Bradley S. Moore

et al.

Natural Product Reports, Journal Year: 2024, Volume and Issue: 41(4), P. 604 - 648

Published: Jan. 1, 2024

Covering: 1997 to 2023The shikimate pathway is the metabolic process responsible for biosynthesis of aromatic amino acids phenylalanine, tyrosine, and tryptophan. Seven steps convert phosphoenolpyruvate (PEP) erythrose 4-phosphate (E4P) into ultimately chorismate, which serves as branch point dedicated acid biosynthesis. Bacteria, fungi, algae, plants (yet not animals) biosynthesize chorismate exploit its intermediates in their specialized metabolism. This review highlights diversity derived from along seven PEP E4P well additional sections on compounds prephenate, anthranilate synonymous aminoshikimate pathway. We discuss genomic basis biochemical support leading shikimate-derived antibiotics, lipids, pigments, cofactors, other metabolites across tree life.

Language: Английский

Citations

46
Complete integration of carbene-transfer chemistry into biosynthesis DOI
Jing Huang, Andrew F. G. Quest, Pablo Cruz‐Morales

et al.

Nature, Journal Year: 2023, Volume and Issue: 617(7960), P. 403 - 408

Published: May 3, 2023

Language: Английский

Citations

33
Discovery of the Azaserine Biosynthetic Pathway Uncovers a Biological Route for α‐Diazoester Production DOI Creative Commons
Devon Van Cura, Tai L. Ng, Jing Huang

et al.

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(28)

Published: May 8, 2023

Azaserine is a bacterial metabolite containing biologically unusual and synthetically enabling α-diazoester functional group. Herein, we report the discovery of azaserine (aza) biosynthetic gene cluster from Glycomyces harbinensis. Discovery related clusters reveals previously unappreciated producers, heterologous expression aza confirms its role in assembly. Notably, this encodes homologues hydrazonoacetic acid (HYAA)-producing enzymes, implicating HYAA biosynthesis. Isotope feeding biochemical experiments support hypothesis. These discoveries indicate that 2-electron oxidation hydrazonoacetyl intermediate required for formation, constituting distinct logic diazo Uncovering biological route synthesis now enables production highly versatile carbene precursor cells, facilitating approaches engineering complete carbene-mediated transformations vivo.

Language: Английский

Citations

24
Enzymatic synthesis of azide by a promiscuous N-nitrosylase DOI
Antonio Del Rio Flores, Rui Zhai, David W. Kastner

et al.

Nature Chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 27, 2024

Language: Английский

Citations

7
A Natural Dihydropyridazinone Scaffold Generated from a Unique Substrate for a Hydrazine-Forming Enzyme DOI
Kenichi Matsuda, Kuga Arima,

Satoko Akiyama

et al.

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(28), P. 12954 - 12960

Published: June 30, 2022

Nitrogen–nitrogen bond-containing functional groups are rare, but they found in a considerably wide class of natural products. Recent clarifications the biosynthetic routes for such shed light onto overlooked genes distributed across bacterial kingdom, highlighting presence yet-to-be identified products with peculiar groups. Here, genome-mining approach targeting unique hydrazine-forming gene led to discovery actinopyridazinones A (1) and B (2), first dihydropyridazinone rings. The structure actinopyridazinone was unambiguously established by total synthesis. Biosynthetic studies unveiled structural diversity hydrazines derived from this family N–N bond-forming enzymes.

Language: Английский

Citations

23
Biocatalytic cyclization of small macrolactams by a penicillin-binding protein-type thioesterase DOI

Zachary L. Budimir,

Rishi Patel,

Alyssa S. Eggly

et al.

Nature Chemical Biology, Journal Year: 2023, Volume and Issue: 20(1), P. 120 - 128

Published: Dec. 7, 2023

Language: Английский

Citations

15
Bacterial Avenalumic Acid Biosynthesis Includes Substitution of an Aromatic Amino Group for Hydride by Nitrous Acid Dependent Diazotization DOI
Seiji Kawai, Ryota Hagihara, Kazuo Shin‐ya

et al.

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(45)

Published: Sept. 17, 2022

The diazo group is an important functional that can confer biological activity to natural products owing its high reactivity. Recent studies have revealed groups are synthesized from amino using nitrous acid in secondary metabolites of actinomycetes. However, genome database analysis indicated there still many group-biosynthesizing enzymes for unknown biosynthetic pathways. Here, we discovered avenalumic biosynthesis gene cluster Streptomyces sp. RI-77 by mining involved formation. Through heterologous expression, the was direct (AVA) via 3-aminoavenalumic (3-AAA). In vitro enzyme assays showed AvaA6 and AvaA7 catalyzed diazotization 3-AAA substitution hydride synthesize AVA, respectively. This study unprecedented pathway removal diazotization.

Language: Английский

Citations

21
Identification of the Azaserine Biosynthetic Gene Cluster Implicates Hydrazine as an Intermediate to the Diazo Moiety DOI
Zi-Wang Wei, Haruka Niikura, Menghua Wang

et al.

Organic Letters, Journal Year: 2023, Volume and Issue: 25(22), P. 4061 - 4065

Published: May 26, 2023

Azaserine (1) is a natural product and nonproteinogenic amino acid containing diazo group. Here we report the biosynthetic gene cluster for 1 from Glycomyces harbinensis. We then use isotopic feeding, deletion, biochemical experiments to support pathway whereby hydrazinoacetic (2) peptidyl carrier protein-loaded serine (3) are intermediates on route final 1.

Language: Английский

Citations

11
Identification and Analysis of the Biosynthetic Gene Cluster for the Hydrazide-Containing Aryl Polyene Spinamycin DOI
Seiji Kawai,

Akito Yamada,

Danyao Du

et al.

ACS Chemical Biology, Journal Year: 2023, Volume and Issue: 18(8), P. 1821 - 1828

Published: July 27, 2023

Natural products containing nitrogen-nitrogen (N-N) bonds have attracted much attention because of their bioactivities and chemical features. Several recent studies revealed the nitrous acid-dependent N-N bond-forming machinery. However, catalytic mechanisms hydrazide synthesis using acid remain unknown. Herein, we focused on spinamycin, a hydrazide-containing aryl polyene produced by Streptomyces albospinus JCM3399. In S. genome, discovered putative spinamycin biosynthetic gene (spi) cluster genes that encode type II polyketide synthase for secondary metabolism-specific biosynthesis pathway. A inactivation experiment showed this was responsible biosynthesis. feeding stable isotope-labeled sodium nitrite analysis acid-synthesizing enzymes in vitro strongly indicated one nitrogen atoms group derived from acid. substrate specificity SpiA3, which is loading starter onto synthase, bond formation occurs after loading. AMP-dependent ligase SpiA7 catalyzes diazotization an amino benzene ring without hydroxy group, resulting highly reactive diazo intermediate, may be key step formation. Therefore, propose overall pathway spinamycin. This study expands our knowledge microbial metabolism.

Language: Английский

Citations

11
Structure and mechanism of haem-dependent nitrogen–nitrogen bond formation in piperazate synthase DOI
M.A. Higgins,

Xinjie Shi,

Jordi Soler Soler

et al.

Nature Catalysis, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 13, 2025

Language: Английский

Citations

0