Cloning and Heterologous Expression of the Entire Gene Clusters for PD 116740 from Streptomyces Strain WP 4669 and Tetrangulol and Tetrangomycin from Streptomyces Rimosus NRRL 3016

Overview

Journal J Bacteriol

Publisher American Society for Microbiology

Specialty Microbiology

Date 1997 Jan 1

PMID 8990300

Citations 12

Authors

S T Hong

J R Carney

S J Gould

Affiliations

Soon will be listed here.

Abstract

The genes for the complete pathways for two polycyclic aromatic polyketides of the angucyclinone class have been cloned and heterologously expressed. Genomic DNAs of Streptomyces rimosus NRRL 3016 and Streptomyces strain WP 4669 were partially digested with MboI, and libraries (ca. 40-kb fragments) in Escherichia coli XL1-Blue MR were prepared with the cosmid vector pOJ446. Hybridization with the actI probe from the actinorhodin polyketide synthase genes identified two clusters of polyketide genes from each organism. After transfer of the four clusters to Streptomyces lividans TK24, expression of one cluster from each organism was established through the identification of pathway-specific products by high-performance liquid chromatography with photodiode array detection. Peaks were identified from the S. rimosus cluster (pksRIM-1) for tetrangulol, tetrangomycin, and fridamycin E. Peaks were identified from the WP 4669 cluster (pksWP-2) for tetrangulol, 19-hydroxytetrangulol, 8-O-methyltetrangulol, 19-hydroxy-8-O-methyltetrangulol, and PD 116740. Structures were confirmed by 1H nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry.

Citing Articles

Integrative metabolo-genomics suggests a biosynthetic pathway for tetrangulol in Streptomyces sp. KL110A.

Trejo-Alarcon L, Cano-Prieto C, Calheiros de Carvalho A, Rago D, Ahonen L, Cruz-Morales P World J Microbiol Biotechnol. 2025; 41(3):101.

PMID: 40064729 PMC: 11893679. DOI: 10.1007/s11274-025-04298-7.

Co-expression of a pair of interdependent regulators coding genes ovmZ and ovmW awakens the production of angucyclinones antibiotics in Streptomyces neyagawaensis.

Li J, Wang K, Luo S, Tian Y, Li Y, Hu S Microb Cell Fact. 2024; 23(1):202.

PMID: 39026365 PMC: 11264864. DOI: 10.1186/s12934-024-02478-y.

Himalaquinones A-G, Angucyclinone-Derived Metabolites Produced by the Himalayan Isolate sp. PU-MM59.

Zhang Y, Cheema M, Ponomareva L, Ye Q, Liu T, Sajid I J Nat Prod. 2021; 84(7):1930-1940.

PMID: 34170698 PMC: 8565601. DOI: 10.1021/acs.jnatprod.1c00192.

A Natural Product Chemist's Guide to Unlocking Silent Biosynthetic Gene Clusters.

Covington B, Xu F, Seyedsayamdost M Annu Rev Biochem. 2021; 90:763-788.

PMID: 33848426 PMC: 9148385. DOI: 10.1146/annurev-biochem-081420-102432.

spp. From Ethiopia Producing Antimicrobial Compounds: Characterization via Bioassays, Genome Analyses, and Mass Spectrometry.

Kibret M, Guerrero-Garzon J, Urban E, Zehl M, Wronski V, Ruckert C Front Microbiol. 2018; 9:1270.

PMID: 29946312 PMC: 6007079. DOI: 10.3389/fmicb.2018.01270.

References

Gravius B, Bezmalinovic T, Hranueli D, Cullum J . Genetic instability and strain degeneration in Streptomyces rimosus. Appl Environ Microbiol. 1993; 59(7):2220-8. PMC: 182261. DOI: 10.1128/aem.59.7.2220-2228.1993. View

Katz L, Donadio S . Polyketide synthesis: prospects for hybrid antibiotics. Annu Rev Microbiol. 1993; 47:875-912. DOI: 10.1146/annurev.mi.47.100193.004303. View

Fu H, McDaniel R, Hopwood D, Khosla C . Engineered biosynthesis of novel polyketides: stereochemical course of two reactions catalyzed by a polyketide synthase. Biochemistry. 1994; 33(31):9321-6. DOI: 10.1021/bi00197a036. View

McDaniel R, Fu H, Hopwood D, Khosla C . Engineered biosynthesis of novel polyketides: influence of a downstream enzyme on the catalytic specificity of a minimal aromatic polyketide synthase. Proc Natl Acad Sci U S A. 1994; 91(24):11542-6. PMC: 45267. DOI: 10.1073/pnas.91.24.11542. View

Grimm A, Madduri K, Ali A, Hutchinson C . Characterization of the Streptomyces peucetius ATCC 29050 genes encoding doxorubicin polyketide synthase. Gene. 1994; 151(1-2):1-10. DOI: 10.1016/0378-1119(94)90625-4. View

Han L, Yang K, Ramalingam E, Mosher R, VINING L . Cloning and characterization of polyketide synthase genes for jadomycin B biosynthesis in Streptomyces venezuelae ISP5230. Microbiology (Reading). 1994; 140 ( Pt 12):3379-89. DOI: 10.1099/13500872-140-12-3379. View

McDaniel R, Hopwood D, Khosla C . Rational design of aromatic polyketide natural products by recombinant assembly of enzymatic subunits. Nature. 1995; 375(6532):549-54. DOI: 10.1038/375549a0. View

Decker H, Haag S . Cloning and characterization of a polyketide synthase gene from Streptomyces fradiae Tü2717, which carries the genes for biosynthesis of the angucycline antibiotic urdamycin A and a gene probably involved in its oxygenation. J Bacteriol. 1995; 177(21):6126-36. PMC: 177452. DOI: 10.1128/jb.177.21.6126-6136.1995. View

Yu T, Hopwood D . Ectopic expression of the Streptomyces coelicolor whiE genes for polyketide spore pigment synthesis and their interaction with the act genes for actinorhodin biosynthesis. Microbiology (Reading). 1995; 141 ( Pt 11):2779-91. DOI: 10.1099/13500872-141-11-2779. View

10.

Hutchinson C, Fujii I . Polyketide synthase gene manipulation: a structure-function approach in engineering novel antibiotics. Annu Rev Microbiol. 1995; 49:201-38. DOI: 10.1146/annurev.mi.49.100195.001221. View

11.

Blanco G, Fu H, Mendez C, Khosla C, Salas J . Deciphering the biosynthetic origin of the aglycone of the aureolic acid group of anti-tumor agents. Chem Biol. 1996; 3(3):193-6. DOI: 10.1016/s1074-5521(96)90262-8. View

12.

Tsoi C, Khosla C . Combinatorial biosynthesis of 'unnatural' natural products: the polyketide example. Chem Biol. 1995; 2(6):355-62. DOI: 10.1016/1074-5521(95)90214-7. View

13.

Davis N, Chater K . Spore colour in Streptomyces coelicolor A3(2) involves the developmentally regulated synthesis of a compound biosynthetically related to polyketide antibiotics. Mol Microbiol. 1990; 4(10):1679-91. DOI: 10.1111/j.1365-2958.1990.tb00545.x. View

14.

Hopwood D, Sherman D . Molecular genetics of polyketides and its comparison to fatty acid biosynthesis. Annu Rev Genet. 1990; 24:37-66. DOI: 10.1146/annurev.ge.24.120190.000345. View

15.

Rohr J, Thiericke R . Angucycline group antibiotics. Nat Prod Rep. 1992; 9(2):103-37. DOI: 10.1039/np9920900103. View

16.

Bierman M, Logan R, OBrien K, Seno E, Rao R, Schoner B . Plasmid cloning vectors for the conjugal transfer of DNA from Escherichia coli to Streptomyces spp. Gene. 1992; 116(1):43-9. DOI: 10.1016/0378-1119(92)90627-2. View

17.

Fernandez-Moreno M, Martinez E, Boto L, Hopwood D, Malpartida F . Nucleotide sequence and deduced functions of a set of cotranscribed genes of Streptomyces coelicolor A3(2) including the polyketide synthase for the antibiotic actinorhodin. J Biol Chem. 1992; 267(27):19278-90. View

18.

Kuntsmann M, Mitscher L . The structural characterization of tetrangomycin and tetrangulol. J Org Chem. 1966; 31(9):2920-5. DOI: 10.1021/jo01347a043. View

19.

Liu W, Parker L, Slusarchyk S, GREENWOOD G, Grahm S, Meyers E . Isolation, characterization, and structure of rabelomycin, a new antibiotic. J Antibiot (Tokyo). 1970; 23(9):437-41. DOI: 10.7164/antibiotics.23.437. View

20.

Harik S, Sharma V, Wetherbee J, WARREN R, Banerjee S . Adrenergic and cholinergic receptors of cerebral microvessels. J Cereb Blood Flow Metab. 1981; 1(3):329-38. DOI: 10.1038/jcbfm.1981.36. View