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Abstract
The phylum proteobacteria contains a wide array of Gram-negative marine bacteria. With recent advances in genomic sequencing, genome analysis, and analytical chemistry techniques, a whole host of information is being revealed about the primary and secondary metabolism of marine proteobacteria. This has led to the discovery of a growing number of medically relevant natural products, including novel leads for the treatment of multidrug-resistant Staphylococcus aureus (MRSA) and cancer. Of equal interest, marine proteobacteria produce natural products whose structure and biosynthetic mechanisms differ from those of their terrestrial and actinobacterial counterparts. Notable features of secondary metabolites produced by marine proteobacteria include halogenation, sulfur-containing heterocycles, non-ribosomal peptides, and polyketides with unusual biosynthetic logic. As advances are made in the technology associated with functional genomics, such as computational sequence analysis, targeted DNA manipulation, and heterologous expression, it has become easier to probe the mechanisms for natural product biosynthesis. This review will focus on genomics driven approaches to understanding the biosynthetic mechanisms for natural products produced by marine proteobacteria.
Highlights
Natural products have long served as the inspiration for a great number of medicinal compounds.Throughout history, from acetylsalicylic acid to Taxol, many of the world’s most effective medicines have been derived from the products of organisms as diverse as plants, fungi, bacteria, and even mammals [1]
It appears that marine bacteria may display a greater diversity/frequency of non-canonical biosynthetic mechanisms, through non-linear or iterative NRPS activity when compared to terrestrial microorganisms, a greater number of halogenated natural products have been identified from marine sources likely due to the higher concentration of halides in seawater compared to soil [21,22,23]
The specific role of AngG in anguibactin biosynthesis is unclear, it may serve as an alternative aryl carrier protein (ArCP) to that found in AngB
Summary
Natural products have long served as the inspiration for a great number of medicinal compounds. NRPS and PKS pathways appear to deviate significantly from those found in terrestrial bacteria [19,20] It appears that marine bacteria may display a greater diversity/frequency of non-canonical biosynthetic mechanisms, through non-linear or iterative NRPS activity when compared to terrestrial microorganisms, a greater number of halogenated natural products have been identified from marine sources likely due to the higher concentration of halides in seawater compared to soil [21,22,23]. The number of interesting natural products identified from marine proteobacteria has increased significantly over the years, with novel structures and biosynthetic mechanisms being proposed. It will highlight the variety of genetic and biochemical experiments that have enabled the characterization of these novel natural product biosynthetic pathways
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