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Abstract The archipelagic country of Indonesia is populated by the densest marine biodiversity in the world which has created strong global interest and is valued by both Indigenous and European settlements for different purposes. Nearly 1000 chemicals have been extracted and identified. In this review, a systematic data curation was employed to collate bioprospecting related manuscripts providing a comprehensive directory based on publications from 1988 to 2022. Findings with significant pharmacological activities are further discussed through a scoping data collection. This review discusses macroorganisms (Sponges, Ascidian, Gorgonians, Algae, Mangrove) and microorganism (Bacteria and Fungi) and highlights significant discoveries, including a potent microtubule stabilizer laulimalide from Hyattella sp., a prospective doxorubicin complement papuamine alkaloid from Neopetrosia cf exigua, potent antiplasmodial manzamine A from Acanthostrongylophora ingens, the highly potent anti trypanosomal manadoperoxide B from Plakortis cfr. Simplex, mRNA translation disrupter hippuristanol from Briareum sp, and the anti-HIV-1 (+)-8-hydroxymanzamine A isolated from Acanthostrongylophora sp. Further, some potent antibacterial extracts were also found from a limited biomass of bacteria cultures. Although there are currently no examples of commercial drugs from the Indonesian marine environment, this review shows the molecular diversity present and with the known understudied biodiversity, reveals great promise for future studies and outcomes. Graphical Abstract

The previously undescribed natural product lumnitzeralactone (1), which represents a derivative of ellagic acid, was isolated from the anti-bacterial extract of the Indonesian mangrove species Lumnitzera racemosa Willd. The structure of lumnitzeralactone (1), a proton-deficient and highly challenging condensed aromatic ring system, was unambiguously elucidated by extensive spectroscopic analyses involving high-resolution mass spectrometry (HRMS), 1D 1H and 13C nuclear magnetic resonance spectroscopy (NMR), and 2D NMR (including 1,1-ADEQUATE and 1,n-ADEQUATE). Determination of the structure was supported by computer-assisted structure elucidation (CASE system applying ACD-SE), density functional theory (DFT) calculations, and a two-step chemical synthesis. Possible biosynthetic pathways involving mangrove-associated fungi have been suggested.

Lumnitzera littorea and Lumnitzera racemosa are mangrove species distributed widely along the Indonesian coasts. Besides their ecological importance, both are of interest owing to their wealth of natural products, some of which constitute potential sources for medicinal applications. We aimed to discover and characterize new anti-infective compounds, based on population-level sampling of both species from across the Indonesian Archipelago. Root metabolites were investigated by TLC, hyphenated LC-MS/MS and isolation, the internal transcribed spacer (ITS) region of rDNA was used for genetic characterization. Phytochemical characterization of both species revealed an unusual diversity in sulfated constituents with 3,3’,4’-tri-O-methyl-ellagic acid 4-sulfate representing the major compound in most samples. None of these compounds was previously reported for mangroves. Chemophenetic comparison of L. racemosa populations from different localities provided evolutionary information, as supported by molecular phylogenetic evidence. Samples of both species from particular locations exhibited anti-bacterial potential (Southern Nias Island and East Java against Gram-negative bacteria, Halmahera and Ternate Island against Gram-positive bacteria). In conclusion, Lumnitzera roots from natural mangrove stands represent a promising source for sulfated ellagic acid derivatives and further sulfur containing plant metabolites with potential human health benefits.