Marine Natural Products Research in South-East Asia

Southeast Asia, a region renowned for its rich marine biodiversity, has emerged as a critical hub for marine natural products (MNPs) research. This introductory chapter provides a comprehensive overview of the current status of marine biotechnology in the region, particularly its application in drug discovery. Key Southeast Asian countries, including Indonesia, Vietnam, Thailand, Malaysia, the Philippines and Singapore, have made notable advancements in exploring marine organisms, such as sponges, tunicates, soft corals, echinoderms and algae, for bioactive compounds. These marine taxa have been shown to yield diverse metabolites with potential pharmacological uses, including antimicrobial, anticancer and anti-inflammatory properties. Despite this potential, the development of marine drug discovery programs across Southeast Asia remains uneven, with disparities in research capacity, infrastructure and international collaboration. The region faces pressing challenges, including overfishing, pollution and climate change, which threaten the very biodiversity it depends upon. Additionally, there are substantial opportunities for leveraging traditional marine medicine knowledge and transitioning toward sustainable blue economy frameworks. This chapter sets the stage for the book by summarizing the marine biotechnological landscape across Southeast Asia, identifying key biodiversity resources, ongoing initiatives, and gaps in knowledge and infrastructure that need to be addressed for future innovation and conservation.

Indonesian marine natural products are diverse, reflecting biodiversity of genes, species, and environment. Through evolution, marine natural products (MNPs) are biosynthesized via multiple enzymatic cascade reactions that can carry out specific biological functions within and/or between organisms. Accordingly, MNP structures can be biologically prevalidated that can be used for drugs, chemical probes, and scientific developments. Skeletons, building blocks, or scaffolds are either conserved or evolved within marine organisms as response to their environment. Although the chemical diversity and significant biological activity can be evaluated, there are possible limitations of the detection methods because of the existence of reactive MNPs. Since 1972, 911 molecules including 879 original MNPs, 4 structures isolated for the first time but known as synthetic entities, 33 structural revisions, 34 artifacts, and 1 proposed MNPs have been discovered. The Indonesian MNPs are approximately sourced from 108 species, 116 genera, 76 families, 37 orders, 17 classes, 12 phyla, and 5 kingdoms. Of the 911 molecules, only 37 MNPs are categorized to have potent biological activities. The chapter covers the structures of organic molecules (original and revised), potent biological activities, their structure determination studies, and supply challenge of talented MNPs from Indonesia.

Marine natural products are a rich source of chemically diverse and biologically active molecules. Over two decades (2001–2024), a total of 228 marine natural products have been reported from soft corals, red algae, sponges and cyanobacteria collected in Malaysia. Malaysia is ranked as the 12^th most biodiverse country in the world and is recognized as one of the world’s megadiverse nations. This chapter focuses on marine natural products isolated from these marine organisms, biological activities, sampling locations, compound isolation workflows, and ¹H and ¹³C nuclear magnetic resonance (NMR) spectroscopy for structure characterizations. In addition, this chapter will also introduce some of the most prominent examples of marine natural products biosynthesis and origin of marine natural products.

The Philippines, an archipelagic nation of over 7100 islands, has one of the longest coastlines in the world and a highly biodiverse marine ecosystem. The rich marine flora and fauna serve diverse purposes, as food, nutraceuticals, cosmetic products, and traditional medicines. Here, we comprehensively describe natural products discoveries from marine organisms in the Philippines over the past 25 years, covering the chemistry and biological activity. We focus on small-molecule compounds and medium-sized peptides from marine invertebrates, plants, and microorganisms within the Philippine Seas. A total of 403 marine natural products are reported, purified from 56 marine genera, with collections done in 30 provinces across the Philippines. Cytotoxicity and potential anticancer activity is a major theme for small molecules from invertebrates and microorganisms. Peptides from marine mollusks and small molecule compounds from mollusk-associated microorganisms have primarily been assessed for neuroactivity and antipain utility. Members of the Phylum Porifera were the most sampled and studied, with more than 200 compounds reported from 23 genera. Among the different marine genera, significant work has been done in the blue sponge Xestospongia sp.,  Conus spp., and Streptomyces spp. from the Philippines, spanning foundational research on organismal biology to in-depth pharmacological studies of bioactive compounds.

Singapore, despite its small size and highly urbanized environment, hosts a remarkable diversity of marine life, including coral reefs, mangroves and seagrass meadows. However, extensive coastal development, pollution and climate change have significantly impacted these ecosystems, leading to habitat loss and biodiversity shifts. This chapter provides an overview of Singapore’s marine biodiversity, current status on marine drug discovery as well as highlights several research initiatives related to marine microbiome as sources of new drug agents. Local marine organisms, such as corals, sponges, tunicates and cyanobacteria, are rich sources of bioactive compounds with pharmaceutical potential, including antimicrobial, anticancer and antiinfective agents. Advances in biotechnology and molecular techniques have enabled researchers to explore the chemical diversity of marine organisms, uncovering novel compounds with applications in medicine, biotechnology and environmental management. The chapter also discusses the challenges facing marine natural products research in Singapore, such as limited marine biodiversity, high research costs and sustainability concerns. To address these challenges, the integration of innovative technologies, including metabolomics, genomics, synthetic biology, and artificial intelligence, is proposed. By balancing ecological protection with scientific innovation, Singapore aims to ensure the long-term viability of its marine resources while contributing to global advancements in marine natural products research.

Thailand, located in Southeast Asia, boasts a rich marine biodiversity characterized by its extensive coastline and unique marine ecosystems. The country’s marine resources, particularly its diverse sponge species, have drawn considerable interest in natural product research due to their potential in pharmaceutical applications. This chapter focuses on sponge-derived marine natural products (MNPs) identified in Thailand, highlighting their chemical diversity and biological activities. The discussion spans terpenoids, steroids, alkaloids and other bioactive compounds, showcasing their roles in combating infections, cancers and other diseases. Research conducted since 1988 has yielded numerous bioactive compounds from Thai sponges, many of which exhibit potent anti-infective, cytotoxic or antimalarial activities. Significant efforts have been directed towards understanding the chemistry and biosynthesis of these metabolites, including semi-synthetic derivatives, to enhance their therapeutic potential. This comprehensive review not only underscores the pharmaceutical promise of Thai marine sponges but also emphasizes the collaborative contributions of Thai and international research teams in the advancement of marine natural products. The findings presented here pave the way for future drug discovery efforts while advocating for the conservation of Thailand’s unique marine ecosystems.

The chapter on marine biodiversity and bioprospecting in Vietnam provides coverage on the taxonomic diversity and distribution as well as range of specialized metabolites reported from benthic marine invertebrates, including sponges, cnidarians and echinoderms. An analysis of the marine biodiversity across Vietnam’s coastal regions, with a focus on sponges, octocorals and echinoderms, will be presented. A total of 291 sponge species have been recorded, predominantly from the class Demospongiae, while extensive surveys reveal diverse octocoral species (220 species, 48 genera) concentrated in the Southeast Coastal Region. Echinoderm diversity is also high, with 345 species documented across five main classes, especially in the Southeast region. Hierarchical clustering and MDS analyses reveal distinct biogeographic patterns, showing close species composition similarity between the Southwest and Southeast regions, while the North Central region maintains unique species characteristics. These biodiversity patterns suggest the influence of ecological and environmental factors on species distribution, highlighting the critical importance of these regions in supporting Vietnam’s rich marine ecosystems. In addition, the chapter covers marine natural products derived from these marine invertebrates reported in literature from 1990 to 2023. It includes discussion on synthetic efforts and molecular targets of selected molecules as drug leads for biomedical applications.

The East Sea region presents a prolific and underexplored source of marine microbial natural products with immense potential for drug discovery and biotechnological applications. The unique ecological conditions of the East Sea, from its diverse Vietnamese coastal ecosystems to remote archipelagos and deep-sea habitats, foster microbial communities capable of producing structurally unique and potent bioactive compounds. This chapter delves into the bioprospecting efforts within this region by focusing on marine microbes, such as bacteria and fungi, and revealing their capacity to produce diverse bioactive compounds, such as alkaloids, peptides, polyketides, terpenoids and steroids. These secondary metabolites exhibit significant pharmacological properties, including antimicrobial, anticancer and anti-inflammatory activities, addressing pressing medical challenges like antibiotic resistance and cancer therapy. Furthermore, the chapter underscores the role of advanced molecular biology and cultivation techniques in isolating and characterizing novel metabolites from marine microorganisms. It also highlights key discoveries, including compounds with promising therapeutic applications, emphasizing the East Sea's importance as a hotspot for natural product research. Moreover, it advocates sustainable and systematic exploration to unlock the full potential of this biodiverse region. By bridging marine ecology and pharmacology, this research enriches the global repository of therapeutic agents and contributes to addressing unmet medical needs in an environmentally conscious manner.

The discovery of new natural products for drug development greatly depends on rich biodiversity, with the marine environment serving as a prime example. Research into marine natural products has led to the development of several clinical drugs and numerous other candidates, some of which are currently undergoing clinical trials. The marine megadiversity of Papua New Guinea represents a vast, yet largely untapped, source of bioactive natural products. In this review, highlighted are a selection of structurally unique natural products derived from PNG sponges and filamentous cyanobacteria, focusing on those with promising biological activity and potential for drug development. Many of the sponge-derived bioactive compounds presented here appear to originate from non-ribosomal peptide and polyketide biosynthesis pathways, indicating a likely microbial origin. It is through international collaborative efforts, with funding support from programmes, such as the Papua New Guinea International Cooperative Biodiversity Groups (ICBGs), the National Cooperative Drug Discovery Program Group (NCDDG), the Natural Sciences and Engineering Research Council of Canada, the Canadian Cancer Society and others that these bioactive molecules were discovered.