Dissertation defence (Biochemistry): MSc Keith Yamada


16.6.2023 at 12.00 - 16.00
MSc Keith Yamada defends his dissertation in Biochemistry entitled “GENOME MINING ACTINOBACTERIA - Eliciting the Production of Natural Products” at the University of Turku on 16 June 2023 at 12.00pm (University of Turku, Pharmacity, Pha1 auditorium, Itäinen Pitkäkatu 4, Turku).

Opponent: Professor Istvan Molnar (VTT Technical Research Centre of Finland)
Custos: Professor Mikko Metsä-Ketelä (University of Turku)

Digital copy of the thesis at UTUPub: https://urn.fi/URN:ISBN:978-951-29-9288-1.


Summary of the Doctoral Dissertation:

Antimicrobial resistance is an imminent threat that is expected to kill 10 million people per year by 2050. Natural products have been a major source of antimicrobial compounds and encompass a chemical space far greater than synthetic chemistry can provide and have evolved over the ages to have biological activities. The natural products produced by Streptomyces have provided us with two-thirds of the antibiotics currently used, as well as chemotherapeutics, antifungals, and immunosuppressants. In recent years, the drug discovery pipeline from Streptomyces has run dry. However, with the advent of modern genomics, we now realize that Streptomyces has the potential to produce new natural products, providing us with the hope of new drug leads.

My doctoral research focused on the concept of eliciting Streptomyces to produce novel natural products; in other words, what triggers the production of natural products. Genome mining provided insight into the genetic potential of Streptomyces to produce natural products. Yet, how to unlock this potential remained elusive. Additional perspectives from ecology, evolution, and regulation evoked the idea that microbe-microbe interactions could be the key. Microscopic observations of the interactions between Streptomyces and yeast suggested that physical contact is essential for elicitation. Genomics, tranomics, and proteomics showed that 31% of the cryptic biosynthetic gene clusters are activated, as well as a suite of enzymes capable of digesting the cell wall of yeast. Arguably, Streptomyces can prey on yeast. The differential regulation of homologous gene clusters further suggested that natural product production is triggered by different ecological needs.

Moreover, a novel antibacterial natural product was identified from a rare Streptomonospora isolate, with the aid of genome mining. Genome mining was also used to identify two new biosynthetic gene clusters, responsible for the production of the antibiotic komodoquinone B.

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