Marine natural products (MNPs) are an important source of biologically active metabolites, particularly for therapeutic agent development after terrestrial plants and nonmarine microorganisms. Sequencing technologies have revealed that the number of biosynthetic gene clusters (BGCs) in marine microorganisms and the marine environment is much higher than expected. Unfortunately, the majority of them are silent or only weakly expressed under traditional laboratory culture conditions. Furthermore, the large proportion of marine microorganisms are either uncultivable or cannot be genetically manipulated. Efficient heterologous expression systems can activate cryptic BGCs and increase target compound yield, allowing researchers to explore more unknown MNPs. When developing heterologous expression of MNPs, it is critical to consider heterologous host selection as well as genetic manipulations for BGCs. In this review, we summarize current progress on the heterologous expression of MNPs as a reference for future research.

Two novel aspochalasins, 20-β-methylthio-aspochalsin Q (named as aspochalasin V), (1) and aspochalasin W (2), were isolated from culture broth of Aspergillus sp., which was found in the gut of a marine isopod Ligia oceanica. The structures were determined on the basis of NMR and mass spectral data analysis. This is the first report about methylthio-substituted aspochalasin derivatives. Cytotoxicity against the prostate cancer PC3 cell line and HCT116 cell line was assayed using the MTT method. Apochalasin V showed moderate activity at IC₅₀ values of 30.4 and 39.2 μM, respectively.

A new cyclopeptide, together with three known amino acid derivatives, was isolated from marine-derived fungus Aspergillus flavipes, which was found in the gut of isopod Ligia oceanica. The novel peptide contains four amino acid units, proline, 5-methoxyanthranilic acid, isoleucine and 3-aminoacrylic acid. Its structure was determined on the basis of NMR, HR-MS and MSⁿ spectral data analysis. The two unusual amino acid residues, 5-methoxyanthranilic acid and 3-aminoacrylic acid, were first found in natural product. The known compound N-benzoyl-phenylalanine methyl ester was first found as fungal metabolite. This is the first report of natural products isolated from marine gut fungi.