Distinguished Professor of Oceanography

Research Interests

  • Chemistry of marine plants, microorganisms and invertebrate animals.
  • Utilization of marine-derived compounds for the treatment of various human diseases, in particular cancer and infectious diseases.

Degrees

  • B.S., California State Polytechnic University
  • M.S., San Jose State University
  • Ph.D., University of California, Riverside

Recent Publications

Hammons, JC, Trzoss L, Jimenez PC, Hirata AS, Costa-Lotufo LV, La Clair JJ, Fenical W.  2019.  Advance of seriniquinone analogues as melanoma agents. Acs Medicinal Chemistry Letters. 10:186-190. AbstractWebsite

Seriniquinone, a marine natural product, displayed potent cytotoxicity and selectivity against melanoma cancer cells. This selectivity, combined with a novel mode of action (MOA), prompted studies to translate a pharmacologically relevant lead. Herein, we report on structure-activity relationships (SARs), and provide a strategy to prepare analogues that retain activity and offer an improved water solubility and isomeric purity. From intermediates made on a gram-scale, derivatives were prepared and evaluated for their antiproliferation activity and melanoma selectivity. Overall these studies provide methods to install side chain motifs that demonstrate a common, and yet unique, biological profile.

Le, TC, Lee EJ, Lee J, Hong A, Yim CY, Yang I, Choi H, Chin J, Cho SJ, Ko J, Hwang H, Nam SJ, Fenical W.  2019.  Saccharoquinoline, a cytotoxic alkaloidal meroterpenoid from marine-derived bacterium Saccharomonospora sp. Marine Drugs. 17 AbstractWebsite

A cytotoxic alkaloidal meroterpenoid, saccharoquinoline (1), has been isolated from the fermentation broth of the marine-derived bacterium Saccharomonospora sp. CNQ-490. The planar structure of 1 was elucidated by 1D, 2D NMR, and MS spectroscopic data analyzes, while the relative configuration of 1 was defined through the interpretation of NOE spectroscopic data. Saccharoquinoline (1) is composed of a drimane-type sesquiterpene unit in combination with an apparent 6,7,8-trihydroxyquinoline-2-carboxylic acid. This combination of biosynthetic pathways was observed for the first time in natural microbial products. Saccharoquinoline (1) was found to have cytotoxicity against the HCT-116 cancer cell line by inducing G1 arrest, which leads to cell growth inhibition.

Shang, Z, Winter JM, Kauffman CA, Yang I, Fenical W.  2019.  Salinipeptins: Integrated genomic and chemical approaches reveal unusual D-amino acid-containing ribosomally synthesized and post-translationally modified peptides (RiPPs) from a Great Salt Lake Streptomyces sp. Acs Chemical Biology. 14:415-425. AbstractWebsite

Analysis of the full genome of an environmentally unique, halotolerant Streptomyces sp. strain GSL-6C, isolated from the Great Salt Lake, revealed a gene cluster encoding the biosynthesis of the salinipeptins, D-amino-acid containing members of the rare linaridin subfamily of ribosomally synthesized and post-translationally modified peptides (RiPPs). The sequence organization of the unmodified amino acid residues in salinipeptins A D (1-4) were suggested by genome annotation, and subsequently, their sequence and post-translational modifications were defined using a range of spectroscopic techniques and chemical derivatization approaches. The salinipeptins are unprecedented linaridins bearing nine D-amino acids, which are uncommon in RiPP natural products and are the first reported in the linaridin subfamily. Whole genome mining of GSL-6C did not reveal any homologues of the reported genes responsible for amino acid epimerization in RiPPs, inferring new epimerases may be involved in the conversion of L- to D-amino acids. In addition, the N-oxide and dimethylimidazolidin-4-one moieties in salinipeptins B and C, which are modified from N,N-dimethylalanine, are unknown in bacterial peptides. The three-dimensional structure of salinipeptin A, possessing four loops generated by significant hydrogen bonding, was established on the basis of observed nuclear Overhauser effect (NOE) correlations. This study demonstrates that integration of genomic information early in chemical analysis significantly facilitates the discovery and structure characterization of novel microbial secondary metabolites.

Zhou, XF, Liang Z, Li KL, Fang W, Tian YX, Luo XW, Chen YL, Zhan ZK, Zhang T, Liao SR, Liu SW, Liu YH, Fenical W, Tang L.  2019.  Exploring the natural piericidins as anti-renal cell carcinoma agents targeting peroxiredoxin 1. Journal of Medicinal Chemistry. 62:7058-7069. AbstractWebsite

Anti-renal cell carcinoma (RCC) agents with new mechanisms of action are urgently needed. Twenty-seven natural products of the piericidin class, including 17 new ones, are obtained from a marine-derived Streptomyces strain, and several of them show strong inhibitory activities against ACHN renal carcinoma cells. By exploring the mechanisms of two representative natural piericidin compounds, piericidin A (PA) and glucopiericidin A (GPA), peroxiredoxin 1 (PRDX1) is detected as a potential target by transcriptome data of PA-treated ACHN cells, as well as the paired RCC tumor versus adjacent nontumor tissues. PA and GPA induce cell apoptosis through reducing the reactive oxygen species level caused by upregulated PRDX1 mRNA and protein level subsequently and exhibit potent antitumor efficacy in nude mice bearing ACHN xenografts, with increasing PRDX1 expression in tumor. The interaction between PA/GPA and PRDX1 was supported by the docking analysis and surface plasmon resonance. Moreover, the translocation of PRDX1 into the nucleus forced by PA/GPA is proposed to be a key factor for the anti-RCC procedure. Piericidins provide a novel scaffold for further development of potent anti-RCC agents, and the new action mechanism of these agents targeting PRDX1 may improve upon the limitations of existing targeted drugs for the treatment of renal cancer.

Ryu, MJ, Wang SH, Kim S, Yang I, Oh DC, Nam SJ, Fenical W.  2019.  Meroindenon and merochlorins E and F, antibacterial meroterpenoids from a marine-derived sediment bacterium of the genus Streptomyces. Organic Letters. 21:5779-5783. AbstractWebsite

Meroterpenoids, meroindenon (1) and merochlorins E (2) and F (3), were isolated from a marine-derived bacterium belonging to the genus Streptomyces. Their chemical structures were established using extensive analysis of MS, UV, ECD, and NMR spectroscopic data. Compounds 1-3 possess a tetrahydroxynaphthalene core and a C-15-isoprene unit. Compounds 2 and 3 exhibited strong antibacterial activities against B. subtilis, K. rhizophila, and S. aureus, with a range of MIC values from 1 to 2 mu g/mL.