ABSTRACT
Synthetic, combinatorial, and computational methods for making novel scaffolds in drug discovery continue to dominate pharmaceutical research despite recent reviews describing that approximately two-thirds of all newly approved drugs are original natural products, natural product derivatives, synthetic compounds utilizing a natural product pharmacophore, or other biologicals.1 Many of these pharmaceuticals were inspired by compounds produced by terrestrial plants, micro organ isms, and the occasional marine micro-or macroorganisms. Terrestrial micro organ isms continue to display pharmacological potential; however, many plants have been well investigated, rendering novel compounds and drugs harder to nd. A promising resource for natural product libraries is unstudied or understudied organisms, such as the marine microbial environment. The world’s oceans cover more than 70% of the earth’s surface and host many diverse habitats, from deep abyssal plains to shallow coastal tide pools. Each of these environments hosts marine organisms cohabitating and interacting both physically and chemically, creating a unique ecosystem. Many of these organisms have been shown to produce biologically interesting chemistry with many
CONTENTS
6.1 Introduction and History ...................................................................................................... 105 6.2 Methods in Marine Microbe Library Development ............................................................. 108
6.2.1 Sources of Microbes ................................................................................................. 108 6.2.2 Isolation and Cultivation ........................................................................................... 110
6.2.2.1 Targeting Free-Living Microorganisms ..................................................... 110 6.2.2.2 Targeting Host-Associated Microorganisms ............................................. 112
6.2.3 Exploiting Microbial Secondary Metabolism .......................................................... 113 6.2.3.1 Culture-Independent Techniques to Promote Compound Discovery ........ 113 6.2.3.2 Culture-Dependent Techniques to Promote Chemical Production ............ 116
6.2.4 Scale-Up Techniques and Screening ........................................................................ 122 6.3 Currently Approved Drugs of Microbial Origin ..................................................................124 6.4 Conclusion and Future Perspectives ..................................................................................... 126 References ...................................................................................................................................... 127
other organisms still largely undiscovered.2 Marine natural product research has largely focused on sessile or slow-moving macroorganisms such as sponges, tunicates, corals, algae, and mollusks, which often lack a physical defense against predation.3 Studies have shown that many of these organisms host large quantities of diverse micro organ isms beyond the free-living microbes within the water column and soil. This has increased efforts toward understanding host-associated marine micro organ isms and their potential role in drug discovery.4
