Dr. Tal Luzzatto Knaan is the head of the Functional Metabolomics lab. She earned her PhD in Biochemistry from the Hebrew University of Jerusalem. As a Vaadia-BARD postdoctoral fellow, she joined the lab of Prof. Pieter C. Dorrestein at the Skaggs School of Pharmacy and Pharmacological Sciences at the University of California, San Diego (UCSD). Her research focused on developing metabolomics-based approach to study microbial chemical communication, and exploring the marine chemical diversity for potential drug discovery. She did her second fellowship with Dr. Daniel Sher at the department of Marine Biology at the University of Haifa, studying the chemical interactions of marine picoplankton. In 2019, she started her own lab combining cutting-edge, multidisciplinary approach to explore the biological role, regulation, diversity and distribution of natural products in microbes and algae, and their potential biotechnological and medicinal applications. Tal is the head of the emerging Interdisciplinary Center for Metabolomics and Natural Products at the University of Haifa and active in the “Homeward Bound” Women in STEMM Leadership initiative.
Functional Metabolomics and Marine Natural Products
Natural products, are small molecules produced by an organism and have various biological roles in nature. Some serve as regulators of cellular processes, some as communication signals and some as defensive molecules that may be utilized in agriculture, biotechnology and medicine. Natural products have an incredibly long history. Traditionally, natural products from plants, animals and microorganisms were the source of virtually all medicinal treatments from folklore and tribal medicine to the era of antibiotics. The marine environment is highly prolific and treasure trove for novel chemistry for potential drug discovery that is largely understudied. We use functional metabolomics approach to explore the spatial and temporal patterns of small molecules to better understand their functional role in marine biological systems. This approach includes the characterization of the chemical space, the targeting of specific molecules to the biosynthesis and regulation.
Microbes have an immense effect on the wellbeing of virtually all living organisms. Microbes are highly social and exist in complex communities with thousands of other organisms, where they engage in a myriad of interactions that are mediated by the exchange of molecules. The marine environment presents unexplored interaction and thus unexplored chemistry. Mining the chemistry in marine microbes is in the frontline of bioprospecting for the next generation of antibiotics. We apply mass spectrometry-based metabolomics, transcriptomics and genomics to correlate the chemotype to phenotype for the discovery of compounds and new biological functions.
Like land plants, marine plants are considered to be an overwhelming source of natural products, that act to protect and benefit the plant to thrive in its environment, however are less explored in that context. Marine plants such as algae (blue-green algae and seaweeds) seagrasses and mangrove plants also have an immense ecological role as primary producers in oceans, therefore understanding their metabolomic capacity is of great interest. The composition on natural products is very much dependent on the environmental conditions in a given niche. Hence, key questions we will be interested to ask are: What natural products are produced by the plant? When and where are they expressed? What are their biological/ecological roles? And how can we benefit from them?
1. Luzzatto Knaan, T. (2022), Analytics for Grannies 001: Metabolomics. Analytical Science Advances.
2. Wu Z, Aharonovich D, Roth-Rosenberg D, Weissberg O, Luzzatto-Knaan T, Vogts A, Zoccarato L, Eigemann F, Grossart H-P, Voss M, Follows MJ, and Sher D. (2022) Single-cell measurements and modelling reveal substantial organic carbon acquisition by Prochlorococcus, Nature Microbiology.
3. Nahor O, Luzzatto-Knaan T#, Israel A#. (2022) A new genetic lineage of Asparagopsis taxiformis (Rhodophyta) in the Mediterranean Sea: as the DNA barcoding indicates a recent Lessepsian introduction. Frontiers in Marine Sciences. #Denote correspondence https://doi.org/10.3389/fmars.2022.873817
4. Fares Amer N and Luzzatto-Knaan T. (2022) Natural products of marine origin for the treatment of colorectal and pancreatic cancers: mechanisms and potential. International Journal of Molecular Sciences.
5. Librizzi V, Malacrinò A, Li Destri Nicosia MG, Barger N, Luzzatto-Knaan T, Pangallo S, Agosteo GE, Schena L. (2022) Extracts from Environmental Strains of Pseudomonas spp. Effectively Control Fungal Plant Diseases. Plants. 11(3):436. https://doi.org/10.3390/plants11030436
6. Ding L, Bar-Shalom R, Aharonovich D, Kurisawa N, Patial G, Li S, He S, Yan X, Iwasaki A, Suenaga K, Zhu C, Luo H, Tian F, Fares F, Naman CB Luzzatto-Knaan T. (2021) Metabolomic characterization of a cf. Neolyngbya cyanobacterium from the South China Sea reveals Wenchangamide A, a lipopeptide with in vitro apoptotic potential in colon cancer cells. Marine drugs 19(7): 397. https://doi.org/10.3390/md19070397
7. Iwasaki A, Kurisawa N, Wang T, Li X, Luo H, Zhu C, Patial G, Yan X, He S, Luzzatto-Knaan T, Tian F, Naman CB, Suenaga K. (2021) Lingaoamide, a cyclic heptapeptide from a Chinese freshwater cyanobacterium Oscillatoria sp. Tetrahedron Letters. https://doi.org/10.1016/j.tetlet.2021.153214.
8. Roth-Rosenberg D*, Aharonovich D*, Luzzatto-Knaan T*, Vogts A, Zoccarato L, Eigemann F, Nago N, Grossart HP, Voss M and Sher D. (2020) Prochlorococcus rely on microbial interactions rather than on chlorotic resting stages to survive long-term stress. mBio. *Denote equal contribution
9. Cao L, Gurevich A, Alexander KL, Naman CB, Leao T, Glukhov E, Luzzatto-Knaan T, Vargas F, Quinn R, Bouslimani A, Nothias LF, Singh NK, Sanders JG, Benitez RAS, Thompson LR, Hamid MN, Morton JT, Mikheenko A, Shlemov A, Korobeynikov A, Friedberg I, Knight R, Venkateswaran K, Gerwick WH, Gerwick L, Dorrestein PC, Pevzner PA and Mohimani H. (2019) MetaMiner: A scalable peptidogenomics approach for discovery of ribosomal peptide natural products with blind modifications from microbial communities, Cell Systems. https://doi.org/10.1016/j.cels.2019.09.004
10. Melnik A, Vasquez-Baeza Y, Aksenov AA, Hyde E, McAvoy A, Wang M, Silva R, Protsyuk I, Wu J, Bouslimani A, Lim YW, Luzzatto-Knaan T, Comstock, W, Quinn RA, Wong R, Humphrey G, Ackermann G, Spivey T, Brouha SS, Bandeira N, Lin GY, Rohwer FL, Conrad DJ, Alexandrov T, Knight R, Dorrestein PC and Garg N. (2019) The molecular and microbial microenvironments in chronically diseased lungs associated with cystic fibrosis. mSystems
11. Luzzatto-Knaan T, Melnik AV and Dorrestein PC. Mass spectrometry uncovers the role of surfactin as an interspecies recruitment factor. (2019) ACS Chemical Biology 14: 459-467.
12. Bouslimani A, da Silva R, Kosciolek T, Janssen S, Amir A, Callewaert C, Dorrestein K, Zaramela L, Kim JN, Humphrey G, Schwartz T, Sanders K, Brennan C, Melnik AV, Luzzatto-Knaan T, Ackermann G, Zengler K, Knight R and Dorrestein PC. The impact of skin care products on skin chemistry and microbiome. (2019) BMC Biology 17 (1):47.
13. Kapono CA, Morton JT, Bouslimani A, Melnik AV, Orlinsky K, Luzzatto-Knaan T, Garg N, Vázquez-Baeza Y, Protsyuk I, Janssen S, Zhu Q, Alexandrov T, Smarr L, Knight R and Dorrestein PC. (2018) Creating a 3D microbial and chemical snapshot of a human habitat. Scientific Reports. 8(1):3669.
14. Luzzatto-Knaan T, Garg N, Wang M, Glukhov E, Peng Y, Ackerman G, Amir A, Duggan BM, Ryazanov S, Gerwick L, Knight R, Alexandrov T, Bandeira N, Gerwick WH and Dorrestein PC. (2017) Digitizing mass spectrometry data to explore the chemical diversity and distribution of marine cyanobacteria and algae. eLife. https://doi.org/10.7554/eLife.24214.001
15. Garg N, Luzzatto-Knaan T, Melnik AV, Caraballo-Rodríguez AM, Floros DJ, Petras D, Gregor R, Dorrestein PC, Phelan VV. (2016). Natural products as mediators of disease. Natural Product Reports. 34:194-219.
16. Garg N, Zeng Y, Melnik AV, Edlund A, Sanchez LM, Mohimani H, Gurevich A, Miao V, Schiffler S, Lim YW, Luzzatto-Knaan T, Cai S, Rohwer F, Pevzner PA, Cichewicz RH, Alexandrov T and Dorrestein PC. (2016) Molecular architecture of the microbial community of Peltigera lichen. mSystems. 1(6). pii: e00139-16.
17. Petras D, Nothias LF, Quinn RA, Alexandrov T, Bandeira N, Bouslimani A, Castro-Falcón G, Chen L, Dang T, Floros DJ, Hook VY, Garg N, Hoffner N, Jiang Y, Kapono CA, Koester I, Knight R, Leber CA, Ling TJ, Luzzatto-Knaan T, McCall LI, McGrath AP, Meehan MJ, Merritt JK, Mills RH, Morton J, Podvin S, Protsyuk I, Purdy T, Satterfield K, Searles S, Shah S, Shires S, Steffen D, White M, Todoric J, Tuttle R, Wojnicz A, Sapp V, Vargas F, Yang J, Zhang C and Dorrestein PC. (2016) Mass spectrometry-based visualization of molecules associated with human habitats. Analytical Chemistry. 88:10775-10784.
18. Wang M, Carver J, Phelan VV, Sanchez LM, Garg N, Peng Y, Watrous J, Nguyen D, Kapono CA, Luzzatto-Knaan T, Porto C, Bouslimani A, Melnik AV, Meehan MJ, Liu WT, Crusemann M, Boudreau PD, Esquenazi E, Sandoval-Calderon M, Kersten RD, Pace LA, Quinn RA, Duncan KR, Hsu CC, Floros DJ, Gavilan RG, Kleigrewe K, Northen T, Dutton RJ, Parrot D, Carlson EE, Aigle B, Michelsen CF, Jelsbak L, Sohlenkamp C, Pevzner P, Edlund A, McLean J, Piel J, Murphy BT, Gerwick L, Liaw CC, Yang YL, Humpf HU, Maansson M, Keyzers RA, Sims AC, Johnson AR, Sidebottom AM, Sedio BE, Klitgaard A, Larson CB, Boya PC, Torres-Mendoza D, Gonzalez DJ, Silva DB, Marques LM, Demarque DP, Pociute E, O’Neill EC, Briand E, Helfrich EJ, Granatosky EA, Glukhov E, Ryffel F, Houson H, Mohimani H, Kharbush JJ, Zeng Y, Vorholt JA, Kurita KL, Charusanti P, McPhail KL, Nielsen KF, Vuong L, Elfeki M, Traxler MF, Engene N, Koyama N, Vining OB, Baric R, Silva RR, Mascuch SJ, Tomasi S, Jenkins S, Macherla V, Hoffman T, Agarwal V, Williams PG, Dai J, Neupane R, Gurr J, Rodriguez AM, Lamsa A, Zhang C, Dorrestein K, Duggan BM, Almaliti J, Allard PM, Phapale P, Nothias LF, Alexandrov T, Litaudon M, Wolfender JL, Kyle JE, Metz TO, Peryea T, Nguyen DT, VanLeer D, Shinn P, Jadhav A, Muller R, Waters KM, Shi W, Liu X, Zhang L, Knight R, Jensen PR, Palsson BO, Pogliano K, Linington RG, Gutierrez M, Lopes NP, Gerwick WH, Moore BS, Dorrestein PC and Bandeira N. (2016) Sharing and community curation of mass spectrometry data with Global Natural Products Social Molecular Networking. Nature Biotechnology. 34:828–837.
19. Luzzatto-Knaan T, Melnik AV and Dorrestein PC. (2015) Mass spectrometry tools and workflows for revealing microbial chemistry. Analyst. 140:4949-4966.
20. Luzzatto Knaan T, Kerem Z, Doron-Faigenboim A and Yedidia I. (2014) Priming of protein expression in the defense response of Zantedeschia aethiopica to Pectobacterium carotovorum. Molecular Plant Pathology.15:364-378.
21. Luzzatto Knaan T, Kerem Z, Lipsky A and Yedidia I. (2013) A systemic response of geophytes is demonstrated by patterns of protein expression and the accumulation of signal molecules in Zantedeschia aethiopica. Plant Physiology and Biochemistry. 71:218-225.
22. Tun OM, Lipsky A, Luzzatto Knaan T, Kerem Z and Yedidia I. (2012) The plant activator BTH promotes Ornithogalum dubium and O. thyrsoides differentiation and regeneration in vitro. Biologia Plantarum. 57:41-48.
23. Luzzatto Knaan T and Yedidia I. (2009) Induction of disease resistance in ornamental geophytes. Israel Journal of Plant Science. 57:401-410.
24. Golan A, Kerem Z, Tun OM, Luzzatto T, Lipsky A and Yedidia I. (2009) Combining flow cytometry and gfp reporter gene for quantitative evaluation of soft- rot bacteria in Ornithogalum dubium plantlets. Journal of Applied Microbiology. 108:1136-1144.
25. Yishay M, Burdman S, Valverde A, Luzzatto T, Ophir R and Yedidia I. (2008) Differential pathogenicity and genetic diversity among Pectobacterium carotovorum subsp. carotovorum isolates from monocot and dicot hosts support early genomic divergence within this taxon. Environmental Microbiology. 10: 2746–2759.
26. Luzzatto T, Golan A, Yishay M, Bilkis I and Yedidia I. (2007) Priming of antimicrobial phenolics during induced resistance response towards Pectobacterium carotovorum in the ornamental monocot calla lily. Journal of Agricultural and Food Chemistry. 55: 10315-10322.
27. Luzzatto T, Yishay M, Lipsky A, Ion A, Belausov E and Yedidia I. (2007) Efficient, long-lasting resistance against the soft rot bacterium Pectobacterium carotovorum in calla lily provided by the plant activator methyl jasmonate. Plant Pathology. 56: 692-701.
Cover page: Plant Pathology. (2007) 56: August issue.
28. Nerya O, Ben-Arie R, Luzzatto T, Musa R, Khativ S and Vaya J. (2006) Prevention of Agaricus bisporus postharvest browning with tyrosinase inhibitors. Postharvest Biology and Technology. 39:272–277.