Polymer degrading marine Microbulbifer bacteria: an un(der)utilized source of chemical and biocatalytic novelty

Introduction

Microbial natural products represent an important reservoir for drug discovery and along with their (semi)synthetic derivatives, constitute a major component of the contemporary pharmaceutical arsenal. Their thusly validated utility is juxtaposed against the barriers to natural product discovery; high rediscovery rates, reliance on largely serendipitous response in bioactivity assays, and the resources and expertise required for their structure determination being the primary impediments . With this background, accessing biological sources that have not yet been extensively mined for natural product discovery is a promising route, one which, at the very least, promises to ameliorate the problem of continued rediscovery of known natural products. This review outlines the recent progress that has been realized using bacteria of the genus Microbulbifer. Together with the emerging field of natural product discovery from Microbulbifer bacteria, this genus of obligate marine bacteria is well validated to be a valuable source of biopolymer degrading enzymes. In this review, we outline the discovery of Microbulbifer enzymes that have substantial biocatalytic potential as it pertains to biopolymer degradation, followed by a description of natural product discovery from this genus.

Microbulbifer is a genus of rod-shaped, aerobic Gram-negative Alteromonadaceae family γ-proteobacteria. They are halophilic obligate marine bacteria that are frequently isolated from diverse marine holobionts such as sponges , sediments , algae , and corals using media that mimic the native salt water habitat. Strains of this genus are detected together with Pseudovibrio and Ruegeria strains that grow in identical culture conditions, and hence obtaining axenic Microbulbifer strains may require repeated rounds of serial enrichment. This genus was first described by Gonzales et al. in 1997 . More than 130 strains have been reported from regions of wide geographical dispersion (Table 1, Figure 1). Microbulbifer bacteria are well known for their capacity to degrade not only a wide variety of polysaccharides including cellulose, agar, chitin, alginate, and xylan , but also plastics . Progressing from their isolation and cultivation, natural product discovery from Microbulbifer bacteria is starting to gather steam . The major classes of natural products isolated from Microbulbifer to date include alkaloids , fatty acid and polyketides , and non-ribosomally synthesized peptides . These findings validate the potential for secondary metabolite discovery from Microbulbifer genus. This review will cover the distributions and origins of Microbulbifer bacteria strains, degradation enzymes, and secondary metabolite discoveries. A focus is placed on the novel chemical structures reported with reference to their biological activities and the biosynthetic studies they have inspired.

Table 1: Summary of marine sources, geographical locations, and key characteristics of Microbulbifer strains reported in literature.

    Origin Location Key characteristics References 1 Microbulbifer hydrolyticus gen. nov. marine pulp mill USA produces hydrolytic enzymes,
polyethylene degradation 2 Microbulbifer degradans. 2-40 salt marsh USA degrades polysaccharides,
polyserine linkers, chitinase 3 Microbulbifer salipaludis sp. nov. salt marsh Korea –a 4 Microbulbifer arenaceous sp. nov. red sandstone Scotland hydrolyzes chitin, esculin, gelatin, and starch 5 Microbulbifer elongates comb. nov. –a Germany –a 6 Microbulbifer sp. JAMB-A7 sediment Japan β-agarase 7 Microbulbifer sp. JAMB-A94 sediment Japan β-agarase, ι-carrageenase 8 Microbulbifer sp. JAMB-A3 sediment Japan β-agarase 9 Microbulbifer maritimus sp. nov. sediment Korea –a 10 Microbulbifer sp. A4B-17 ascidian Palau produces 4-HBA and
parabens 11 Microbulbifer sp. A4A-72 sponge Palau produces 4-HBA 12 Microbulbifer sp. V296 sponge Yap produces 4-HBA 13 Microbulbifer sp. A4B-20 algae Palau produces 4-HBA 14 Microbulbifer sp. A2C-113 sponge Palau produces 4-HBA 15 Microbulbifer sp. A4A-79 ascidian Palau produces 4-HBA 16 Microbulbifer sp. AM222 sediment Palau produces 4-HBA 17 Microbulbifer sp. AM292 sediment Palau produces 4-HBA 18 Microbulbifer sp. A4A-68 sponge Palau produces 4-HBA 19 Microbulbifer sp. A2D-17 sponge Palau produces 4-HBA 20 Microbulbifer sp. I1876 algae Japan produces 4-HBA 21 Microbulbifer sp. C91 algae Yap produces 4-HBA 22 Microbulbifer sp. HG111 sponge Japan produces 4-HBA 23 Microbulbifer sp. F-104 algae Palau produces 4-HBA 24 Microbulbifer sp. V32 sponge Yap produces 4-HBA 25 Microbulbifer sp. HG125 sponge Japan produces 4-HBA 26 Microbulbifer sp. A3G-2 ascidian Palau produces 4-HBA 27 Microbulbifer sp. A3P2-23-3-2 ascidian Palau produces 4-HBA 28 Microbulbifer sp. AM220 sediment Japan produces 4-HBA 29 Microbulbifer sp. YM3-0188 sponge Palau produces 4-HBA 30 Microbulbifer sp. A2D-15 sediment Palau produces 4-HBA 31 Microbulbifer sp. HG869 ascidian Palau produces 4-HBA 32 Microbulbifer sp. HG279 sponge Japan produces 4-HBA 33 Microbulbifer sp. ssthio04PA2-36a sponge Palau produces 4-HBA 34 Microbulbifer celer sp. nov. saltern Korea –a 35 Microbulbifer halophilus sp. nov. saline soil China –a 36 Microbulbifer sp. CMC-5 seaweed India degrades polysaccharides,
β-agarase 37 Microbulbifer variabilis sp. nov. algae Japan –a 38 Microbulbifer epialgicus sp. nov. algae Japan –a 39 Microbulbifer sp. L4-n2 sponge France produces parabens 40 Microbulbifer donghaiensis sp. nov. sediment China –a 41 Microbulbifer chitinilyticus sp. nov. mangrove Japan chitin-degrading 42 Microbulbifer okinawensis sp. nov. mangrove Japan chitin-degrading 43 Microbulbifer sp. SD-1 seawater Korea degrades agar 44 Microbulbifer sp. JAM-3301 sediment Japan inulinase producer 45 Microbulbifer maritimus seaweed India agarase producer 46 Microbulbifer sp. 6532A seaweed Japan alginate lyase producer 47 Microbulbifer marinus sp. nov. sediment China –a 48 Microbulbifer yueqingensis sp. nov. sediment China –a 49 Microbulbifer gwangyangensis sp. nov. tidal flat Korea –a 50 Microbulbifer pacificus sp. nov. sponge Korea –a 51 Microbulbifer mangrove sp. nov. mangrove India polysaccharide-degrading 52 Microbulbifer elongatus HZ11 seawater China seaweed-degrading 53 Microbulbifer thermotolerans DAU221 sediment Korea produces carbohydrate esterase, α-amylase, esterase, chitinase, GH3
-glucosidase polysaccharide lyase 54 Microbulbifer elongatus sp. A13 seaweeds India agarase producer 55 Microbulbifer rhizosphaerae sp. nov. halophytic plant Spain –a 56 Microbulbifer sp. ALW1 algae China produces alginate lyase, laminarinase, β-glucosidase, chondroitinase 57 Microbulbifer flavimaris sp. WRN-8 sediment China –a 58 Microbulbifer mangrovistrain DD-13 mangrove India degrades polysaccharides 59 Microbulbifer echini sp. AM134 sea urchin Korea –a 60 Microbulbifer aggregans sp. CCB-MM1 sediment Malaysia produces sulfite reductase 61 Microbulbifer aestuariivivens sp. GHTF-23 tidal flat Korea –a 62 Microbulbifer sp. Q7 sea cucumber China produces β-agarase, alginate lyases 63 Microbulbifer sp. 127CP7-12 sponge Korea produces violacein 64 Microbulbifer hydrolyticus IRE-31-192 chemical mutation China polyethylene degradation 65 Microbulbifer sp. GL-2 blackfish Japan cellulase 66 Microbulbifer agarilyticus. GP101 invertebrate turbo cornutus Korea –a 67 Microbulbifer sp. BN3 sediment China β-agarase, chitinase

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