A bisprenyl naphthoquinone, phytohabinone (1), and a calcimycin congener with unusual modifications, phytohabimicin (2), were isolated from the culture extract of Phytohabitans sp. RD003013. The structures of 1 and 2 were determined by NMR and MS analyses, and the absolute configuration of 2 was established by using electronic circular dichroism (ECD) calculation. The prenylation pattern of 1 was unprecedented among the known prenylated naphthoquinones. Compound 2 represents a spiroacetal core of polyketide origin substituted with a thiazole carboxylic acid and a dichrolopyrrole moiety, which is an unprecedented modification pattern in the known calcimycin family natural products. Remarkably, 2 showed moderate antimicrobial activity against a Gram-negative bacterium Ralstonia solanacearum while calcimycin was inactive. Additionally, 2 inhibits the migration of EC17 cancer cells at noncytotoxic concentrations.
This is a preview of subscription content, access via your institution
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Rent or buy this article
Prices vary by article type
Prices may be subject to local taxes which are calculated during checkout
Saito S, Indo K, Oku N, Komaki H, Kawasaki M, Igarashi Y. Unsaturated fatty acids and a prenylated tryptophan derivative from a rare actinomycete of the genus Couchioplanes. Beilstein J Org Chem. 2021;17:2939–49.
Lu S, Harunari E, Oku N, Igarashi Y. Trehangelin E, A bisacyl trehalose with plant growth promoting activity from a rare actinomycete Polymorphospora sp. RD064483. J Antibiot. 2022;75:296–300.
Saito S, Oku N, Igarashi Y. Mycetoindole. An N-acyl dehydrotryptophan with plant growth inhibitory activity from an actinomycete of the genus Actinomycetospora. J Antibiot. 2022;75:44–7.
Inahashi Y, Matsumoto A, Danbara H, Omura S, Takahashi Y. Phytohabitans suffuscus gen. nov., sp. nov., an actinomycete of the family Micromonosporaceae isolated from plant roots. Int J Syst Evol Microbiol. 2010;60:2652–8.
Uchida R, Yokota S, Matsuda D, Matsumoto A, Iwamoto S, Onodera H, Takahashi Y, Tomoda H. Habiterpenol, a novel abrogator of bleomycin-induced G2 arrest in Jurkat cells, produced by Phytohabitans suffuscus 3787-5. J Antibiot. 2014;67:777–81.
Komaki H, Tamura T. Polyketide synthase and nonribosomal peptide synthetase gene clusters in type strains of the genus Phytohabitans. Life. 2020;10:257.
Saito S, Xiaohanyao Y, Zhou T, Nakajima-Shimada J, Tashiro E, Triningsih DW, Harunari E, Oku N, Igarashi Y. Phytohabitols A–C, δ-lactone-terminated polyketides from an actinomycete of the genus Phytohabitans. J Nat Prod. 2022;85:1697–703. https://doi.org/10.1021/acs.jnatprod.2c00137.
Kagamizono T, Hamaguchi T, Ando T, Sugawara K, Adachi T, Osada H. Phosphatoquinones A and B, novel tyrosine phosphatase inhibitors produced by Streptomyces sp. J Antibiot. 1999;52:75–80.
Charan RD, Schlingmann G, Bernan VS, Feng X, Carter GT. Fumaquinone, a new prenylated naphthoquinone from Streptomyces fumanus. J Antibiot. 2005;58:271–4.
Blin K, Shaw S, Kloosterman AM, Charlop-Powers Z, van Wezel GP, Medema MH, Weber T. AntiSMASH 6.0: Improving cluster detection and comparison capabilities. Nucleic Acids Res. 2021;49:W29–W35.
Wu Q, Liang J, Lin S, Zhou X, Bai L, Deng Z, Wang Z. Characterization of the biosynthesis gene cluster for the pyrrole polyether antibiotic calcimycin (A23187) in Streptomyces chartreusis NRRL 3882. Antimicrob Agents Chemother. 2011;55:974–82.
Duran-Sampedro G, Agarrabeitia AR, Garcia-Moreno I, Costela A, Bañuelos J, Arbeloa T, López Arbeloa I, Chiara JL, Ortiz MJ. Chlorinated BODIPYs: surprisingly efficient and highly photostable laser dyes. Eur J Org Chem. 2012;2012:6335–50.
Lacerna NM, Miller BW, Lim AL, Tun JO, Robes J, Cleofas M, Lin Z, Salvador-Reyes LA, Haygood MG, Schmidt EW, Concepcion GP. Mindapyrroles A-C, Pyoluteorin analogues from a shipworm-associated bacterium. J Nat Prod. 2019;82:1024–8.
Purdy TN, Kim MC, Cullum R, Fenical W, Moore BS. Discovery and biosynthesis of tetrachlorizine reveals enzymatic benzylic dehydrogenation via an ortho-quinone methide. J Am Chem Soc. 2021;143:3682–6.
Mazzetti C, Ornaghi M, Gaspari E, Parapini S, Maffioli S, Sosio M, Donadio S. Halogenated spirotetronates from Actinoallomurus. J Nat Prod. 2012;75:1044–50.
Murray LAM, Mckinnie SMK, Moore BS, George JH. Meroterpenoid natural products from Streptomyces bacteria-the evolution of chemoenzymatic syntheses. Nat Prod Rep. 2020;37:1334–66.
Chaney MO, Demarco PV, Jones ND, Occolowitz JL. The Structure of A23187, a divalent cation ionophore. J Am Chem Soc. 1974;96:1932–3.
David L, Kergomard A. Production by controlled biosynthesis of a novel ionophore antibiotic, cezomycin (demethylamino a23187). J Antibiot. 1982;35:1409–11.
Liu CM, Chin M, Prosser BL, Palleroni NJ, Westley JW, Miller PA. X-14885A, a novel divalent cation ionophore produced by a streptomyces culture: discovery, fermentation, biological as well as ionophore properties and taxonomy of the producing culture. J Antibiot. 1983;36:1118–22.
Cullen WP, Celmer WD, Chappel LR, Huang LH, Jefferson MT, Ishiguro M, Maeda H, Nishiyama S, Oscarson JR, Shibakawa R, Tone J. CP-61,405, a novel polycyclic pyrrolether antibiotic produced by Streptomyces routienii Huang sp. nov. J Ind Microbiol. 1988;2:349–57.
Yaginuma S, Awata M, Muto N, Kinoshita K, Mizuno K. A novel polyether antibiotic, AC7230 (3-hydroxycezomycin or its stereoisomer). J Antibiot. 1987;40:239–41.
Klika KD, Haansuu JP, Ovcharenko VV, Haahtela KK, Vuorela PM, Sillanpää R. Frankiamide: a structural revision to demethyl (C-11) cezomycin. Z fur Naturforsch-Sect B J Chem Sci. 2003;58:1210–15.
MacroModel, Schrödinger, LLC: New York, NY, 2020.
Gaussian 16, Revision C.01; Gaussian, Inc.: Wallingford, CT, 2016.
Nakae K, Yoshimoto Y, Sawa T, Homma Y, Hamada M, Takeuchi T, Imoto M. Migrastatin, a new inhibitor of tumor cell migration from Streptomyces sp. MK929-43F1. Taxonomy, fermentation, isolation and biological activities. J Antibiot. 2000;53:1130–6.
Sharma AR, Harunari E, Oku N, Matsuura N, Trianto A, Igarashi Y. Two antibacterial and PPARα/γ-agonistic unsaturated keto fatty acids from a coral-associated actinomycete of the genus Micrococcus. Beilstein J Org Chem. 2020;16:297–304.
P388 cells were obtained from JCRB Cell Bank under accession code JCRB0017 (Lot. 06252002). This research was supported by JSPS KAKENHI grant no. JP19K05848 to Y. I.
Conflict of interest
The authors declare no competing interests.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Harunari, E., Mae, S., Fukaya, K. et al. Bisprenyl naphthoquinone and chlorinated calcimycin congener bearing thiazole ring from an actinomycete of the genus Phytohabitans. J Antibiot 75, 542–551 (2022). https://doi.org/10.1038/s41429-022-00559-x
This article is cited by
Species-specific secondary metabolism by actinomycetes of the genus Phytohabitans and discovery of new pyranonaphthoquinones and isatin derivatives
The Journal of Antibiotics (2023)
Isolation and structure determination of allopteridic acids A–C and allokutzmicin from an unexplored actinomycete of the genus Allokutzneria
The Journal of Antibiotics (2023)
Development of a drug discovery approach from microbes with a special focus on isolation sources and taxonomy
The Journal of Antibiotics (2023)