Cyanobacteria are rich secondary metabolite producers. This is evidenced by the large number of natural products reported from these organisms and by the presence of multiple biosynthetic gene clusters (BGCs) in their genomes. In line with what is observed for most bacteria, cyanobacterial BGCs greatly outnumber the reported natural products for this phylum. These observations highlight the potential for discovery of new natural products from cyanobacteria, but they also underscore the lack of effective tools for revealing the natural products associated with orphan BGCs (i.e. those for which no compound can be ascribed). Deorphanizing BGCs from bacteria has been one of the main challenges in natural products discovery ever since next generation sequencing became available at large. For many natural products-rich organisms, genetic tools and appropriate heterologous hosts are readily available to reach this goal. However, modifying cyanobacterial genomes, in particular of non-model strains, is a slow and complicated process, even if possible. Heterologous expression of whole cyanobacterial BGCs in a non-cyanobacterial host has long been considered as a valid strategy, but has progressed slowly, in particular due to challenges in finding suitable hosts. Nevertheless, it has been possible to express over a dozen cyanobacterial BGCs, in particular small-sized clusters, in E coli or cyanobacterial hosts. Direct Pathway Cloning (DiPaC) is a recently developed strategy for BGC capture and heterologous expression that has shown promise in the expression of cyanobacterial BGCs, including complex polyketide synthase (PKS)/non-ribosomal peptide synthetase (NRPS) pathways. Microginins are a large group of over 80 cyanobacterial secondary metabolites. Their structures can be summarized as linear lipopeptides featuruing a 3-amino fatty acyl residue connected to a peptide (typically three or four amino acid residues). Modifications of the fatty acyl residue such as terminal halogenation, hydroxylation or N-methylation are common. Several microginins were shown to inhibit a variety of proteases with considerable potency. Rounge et al proposed that microginin production is carried out by enzymes encoded in the mic BGC (Fig. ), found in the genome of the oscillaginin (a type of microginin)-producing strain Planktothrix prolifica NIVA-CYA 98. This proposal was grounded on the predicted functions of the mic genes, which were consistent with the generation of a metabolite with structure similar to oscillaginins A and B. Specifically, the presence of NRPS adenylation domains whose predicted specificity matched the amino acids found in the oscillaginins, and co-linearity between such adenylation and the sequence of amino acids in these peptides formed the basis for the proposal. However, the mic BGC reported by Rounge et al. with a single PKS module and three NRPS modules could not explain the origin of the Ahda moiety in oscillaginins. Later, Kramer et al. reported a fatty acyl AMP-ligase (FAAL) enzyme associated with a M. aeruginosa mic BGC and proposed that it would activate and load octanoic acid onto an acyl carrier protein (ACP), which would then interact with the PKS module to generate the Ahda residue. The biosynthetic origin of the halogenations that are often observed in microginins was proposed only after the discovery of dimetal carboxylate halogenases -Nakamura et al. identified one putative halogenase of this type within a mic BGC 1.6×10 1.5×10 5.3×10 Organic extract of M. aeruginosa LEGE 91341