Biosynthesis and Genome Mining Potentials of Nucleoside Natural Products

Overview

Journal Chembiochem

Specialty Biochemistry

Date 2023 Jun 26

PMID 37357819

Authors

Yanan Du

Anyarat Thanapipatsiri

Kenichi Yokoyama

Affiliations

Soon will be listed here.

Abstract

Nucleoside natural products show diverse biological activities and serve as leads for various application purposes, including human and veterinary medicine and agriculture. Studies in the past decade revealed that these nucleosides are biosynthesized through divergent mechanisms, in which early steps of the pathways can be classified into two types (C5' oxidation and C5' radical extension), while the structural diversity is created by downstream tailoring enzymes. Based on this biosynthetic logic, we investigated the genome mining discovery potentials of these nucleosides using the two enzymes representing the two types of C5' modifications: LipL-type α-ketoglutarate (α-KG) and Fe-dependent oxygenases and NikJ-type radical S-adenosyl-L-methionine (SAM) enzymes. The results suggest that this approach allows discovery of putative nucleoside biosynthetic gene clusters (BGCs) and the prediction of the core nucleoside structures. The results also revealed the distribution of these pathways in nature and implied the possibility of future genome mining discovery of novel nucleoside natural products.

References

McErlean M, Liu X, Cui Z, Gust B, Van Lanen S . Identification and characterization of enzymes involved in the biosynthesis of pyrimidine nucleoside antibiotics. Nat Prod Rep. 2021; 38(7):1362-1407. PMC: 9483940. DOI: 10.1039/d0np00064g. View

Ohnuki T, Muramatsu Y, Miyakoshi S, Takatsu T, Inukai M . Studies on novel bacterial translocase I inhibitors, A-500359s. IV. Biosynthesis of A-500359s. J Antibiot (Tokyo). 2003; 56(3):268-79. DOI: 10.7164/antibiotics.56.268. View

Huang Y, Liu X, Cui Z, Wiegmann D, Niro G, Ducho C . Pyridoxal-5'-phosphate as an oxygenase cofactor: Discovery of a carboxamide-forming, α-amino acid monooxygenase-decarboxylase. Proc Natl Acad Sci U S A. 2018; 115(5):974-979. PMC: 5798378. DOI: 10.1073/pnas.1718667115. View

Yang Z, Chi X, Funabashi M, Baba S, Nonaka K, Pahari P . Characterization of LipL as a non-heme, Fe(II)-dependent α-ketoglutarate:UMP dioxygenase that generates uridine-5'-aldehyde during A-90289 biosynthesis. J Biol Chem. 2011; 286(10):7885-7892. PMC: 3048675. DOI: 10.1074/jbc.M110.203562. View

Draelos M, Thanapipatsiri A, Sucipto H, Yokoyama K . Cryptic phosphorylation in nucleoside natural product biosynthesis. Nat Chem Biol. 2020; 17(2):213-221. PMC: 7855722. DOI: 10.1038/s41589-020-00656-8. View

Carrasco L, Vazquez D . Molecular bases for the action and selectivity of nucleoside antibiotics. Med Res Rev. 1984; 4(4):471-512. DOI: 10.1002/med.2610040403. View

Kaysser L, Siebenberg S, Kammerer B, Gust B . Analysis of the liposidomycin gene cluster leads to the identification of new caprazamycin derivatives. Chembiochem. 2009; 11(2):191-6. DOI: 10.1002/cbic.200900637. View

He N, Wu P, Lei Y, Xu B, Zhu X, Xu G . Construction of an octosyl acid backbone catalyzed by a radical -adenosylmethionine enzyme and a phosphatase in the biosynthesis of high-carbon sugar nucleoside antibiotics. Chem Sci. 2017; 8(1):444-451. PMC: 5365060. DOI: 10.1039/c6sc01826b. View

Hamma T, Ferre-DAmare A . Pseudouridine synthases. Chem Biol. 2006; 13(11):1125-35. DOI: 10.1016/j.chembiol.2006.09.009. View

10.

Kaysser L, Lutsch L, Siebenberg S, Wemakor E, Kammerer B, Gust B . Identification and manipulation of the caprazamycin gene cluster lead to new simplified liponucleoside antibiotics and give insights into the biosynthetic pathway. J Biol Chem. 2009; 284(22):14987-96. PMC: 2685681. DOI: 10.1074/jbc.M901258200. View

11.

Lin C, McCarty R, Liu H . The biosynthesis of nitrogen-, sulfur-, and high-carbon chain-containing sugars. Chem Soc Rev. 2013; 42(10):4377-407. PMC: 3641179. DOI: 10.1039/c2cs35438a. View

12.

Shiraishi T, Kuzuyama T . Recent advances in the biosynthesis of nucleoside antibiotics. J Antibiot (Tokyo). 2019; 72(12):913-923. DOI: 10.1038/s41429-019-0236-2. View

13.

Goswami A, Liu X, Cai W, Wyche T, Bugni T, Meurillon M . Evidence that oxidative dephosphorylation by the nonheme Fe(II), α-ketoglutarate:UMP oxygenase occurs by stereospecific hydroxylation. FEBS Lett. 2017; 591(3):468-478. PMC: 5380139. DOI: 10.1002/1873-3468.12554. View

14.

Chung B, Mashalidis E, Tanino T, Kim M, Matsuda A, Hong J . Structural insights into inhibition of lipid I production in bacterial cell wall synthesis. Nature. 2016; 533(7604):557-560. PMC: 4882255. DOI: 10.1038/nature17636. View

15.

Cheng L, Chen W, Zhai L, Xu D, Huang T, Lin S . Identification of the gene cluster involved in muraymycin biosynthesis from Streptomyces sp. NRRL 30471. Mol Biosyst. 2010; 7(3):920-7. DOI: 10.1039/c0mb00237b. View

16.

Chi X, Pahari P, Nonaka K, Van Lanen S . Biosynthetic origin and mechanism of formation of the aminoribosyl moiety of peptidyl nucleoside antibiotics. J Am Chem Soc. 2011; 133(36):14452-9. PMC: 3174061. DOI: 10.1021/ja206304k. View

17.

Svidritskiy E, Ling C, Ermolenko D, Korostelev A . Blasticidin S inhibits translation by trapping deformed tRNA on the ribosome. Proc Natl Acad Sci U S A. 2013; 110(30):12283-8. PMC: 3725078. DOI: 10.1073/pnas.1304922110. View

18.

Yokoyama K, Lilla E . C-C bond forming radical SAM enzymes involved in the construction of carbon skeletons of cofactors and natural products. Nat Prod Rep. 2018; 35(7):660-694. PMC: 6051890. DOI: 10.1039/c8np00006a. View

19.

Hong H, Samborskyy M, Zhou Y, Leadlay P . C-Nucleoside Formation in the Biosynthesis of the Antifungal Malayamycin A. Cell Chem Biol. 2019; 26(4):493-501.e5. DOI: 10.1016/j.chembiol.2018.12.004. View

20.

Niu G, Li L, Wei J, Tan H . Cloning, heterologous expression, and characterization of the gene cluster required for gougerotin biosynthesis. Chem Biol. 2013; 20(1):34-44. DOI: 10.1016/j.chembiol.2012.10.017. View