Diversity, Biosynthesis and Bioactivity of Aeruginosins, a Family of Cyanobacteria-Derived Nonribosomal Linear Tetrapeptides

doi:10.3390/md21040217

Review

. 2023 Mar 29;21(4):217.

doi: 10.3390/md21040217.

Diversity, Biosynthesis and Bioactivity of Aeruginosins, a Family of Cyanobacteria-Derived Nonribosomal Linear Tetrapeptides

Jiameng Liu ^{1

2

3}, Mengli Zhang ^{1

2

3}, Zhenkuai Huang ^{1

2

3}, Jiaqi Fang ^{1

2

3}, Zhongyuan Wang ^{1

2

3}, Chengxu Zhou ^{1

2

3}, Xiaoting Qiu ^{1

2

3}

Affiliations

¹ Ministry of Education Key Laboratory of Applied Marine Biotechnology, Ningbo University, Ningbo 315800, China.
² Institute of Marine Biotechnology, College of Food and Pharmaceutical Sciences, Ningbo University, Ningbo 315800, China.
³ Li Dak Sum Yip Yio Chin Kenneth Li Marine Biopharmaceutical Research Center, Ningbo University, Ningbo 315800, China.

PMID: 37103356
PMCID: PMC10143770
DOI: 10.3390/md21040217

Review

Diversity, Biosynthesis and Bioactivity of Aeruginosins, a Family of Cyanobacteria-Derived Nonribosomal Linear Tetrapeptides

Jiameng Liu et al. Mar Drugs. 2023.

. 2023 Mar 29;21(4):217.

doi: 10.3390/md21040217.

Authors

Jiameng Liu ^{1

2

3}, Mengli Zhang ^{1

2

3}, Zhenkuai Huang ^{1

2

3}, Jiaqi Fang ^{1

2

3}, Zhongyuan Wang ^{1

2

3}, Chengxu Zhou ^{1

2

3}, Xiaoting Qiu ^{1

2

3}

Affiliations

¹ Ministry of Education Key Laboratory of Applied Marine Biotechnology, Ningbo University, Ningbo 315800, China.
² Institute of Marine Biotechnology, College of Food and Pharmaceutical Sciences, Ningbo University, Ningbo 315800, China.
³ Li Dak Sum Yip Yio Chin Kenneth Li Marine Biopharmaceutical Research Center, Ningbo University, Ningbo 315800, China.

PMID: 37103356
PMCID: PMC10143770
DOI: 10.3390/md21040217

Abstract

Aeruginosins, a family of nonribosomal linear tetrapeptides discovered from cyanobacteria and sponges, exhibit in vitro inhibitory activity on various types of serine proteases. This family is characterized by the existence of the 2-carboxy-6-hydroxy-octahydroindole (Choi) moiety occupied at the central position of the tetrapeptide. Aeruginosins have attracted much attention due to their special structures and unique bioactivities. Although many studies on aeruginosins have been published, there has not yet been a comprehensive review that summarizes the diverse research ranging from biogenesis, structural characterization and biosynthesis to bioactivity. In this review, we provide an overview of the source, chemical structure as well as spectrum of bioactivities of aeruginosins. Furthermore, possible opportunities for future research and development of aeruginosins were discussed.

Keywords: Choi; aeruginosins; biogenesis; nonribosomal polypeptide synthesis; serine protease inhibitory activity; structural diversity.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1

Figure 1

Structures of aeruginosin 298A, 98A and 98B.

Figure 2

Figure 2

Structures of aeruginosin 98C, 298B, 101, 89A, 89B, and microcin SF608.

Figure 3

Figure 3

Structures of aeruginosin GE686, GE766, GE730, GE810, GE642 and KY642.

Figure 4

Figure 4

Structures of aeruginosin DA688, 205A and 205B.

Figure 5

Figure 5

Structures of oscillarin and aeruginosin 865.

Figure 6

Figure 6

Structures of varlaxin 1046-A, 1022-A, and suomilide.

Figure 7

Figure 7

Structures of dysinosin A-D, chlorodysinosin A and aeruginosin KT608A.

Figure 8

Figure 8

The general structure of aeruginosin.

Figure 9

Figure 9

Structures of aeruginosin 686A and 686B.

Figure 10

Figure 10

A canonical peptide chain extension process during biosynthesis of aeruginosin. (A) Pantoyl–thioglyamine (Ppant) arm is tethered in the PCP domain, which is catalyzed by PPTase; (B) amino acid substrate is activated by A domain and is loaded onto the PCP domain, resulting in the aminoacyl–S-carrier complex; (C) peptide bond formation catalyzed by C domain. PPTase: 4′-phosphopantetheinyl transferase; A: adenylation domain; C: condensation domain; PCP: peptidyl carrier protein domain; CoA: coenzyme A; 3′,5′-ADP: adenosine 3′,5′-diphosphate; ATP: adenosine triphosphate; PPi: pyrophosphoric acid.

Figure 11

Figure 11

The reaction process of the loading of α-keto acid. A: adenylation domain; KR: ketoreductase domain; PCP: peptidyl carrier protein domain; NADPH: nicotinamide adenine dinucleotide phosphate.

Figure 12

Figure 12

A general biosynthetic scheme of aeruginosin. A: adenylation domain; KR: ketoreductase domain; C: condensation domain; PCP: peptidyl carrier protein domain; E: epimerization domain; R: reductase domain.

Figure 13

Figure 13

Biosynthetic gene clusters (BGCs) and structures of several representative types of aeruginosins: aeruginosin 126A (A), aeruginosin 686A (B), dysinosin B (C), aeruginosin NAL2 (D), aeruginosin 865 (E), suomilide (F), varlaxin 1022A and 1046A (G).

See this image and copyright information in PMC

References

1. Paerl H.W., Millie D.F. Physiological ecology of toxic aquatic cyanobacteria. Phycologiacal. 1996;35:160–167. doi: 10.2216/i0031-8884-35-6S-160.1. - DOI
1. Qin B., Li W., Zhu G., Wu T., Gao G. Cyanobacterial bloom management through integrated monitoring and forecasting in large shallow eutrophic Lake Taihu. J. Hazard. Mater. 2015;287:356–363. doi: 10.1016/j.jhazmat.2015年01月04日7. - DOI - PubMed
1. Luesch H., Harrigan G.G., Goetz G., Horgen F.D. The Cyanobacterial origin of potent anticancer agents originally isolated from Sea Hares. Curr. Med. Chem. 2002;9:1791–1806. doi: 10.2174/0929867023369051. - DOI - PubMed
1. Ishida K., Okita Y., Mastsuda H., Okino T., Murakami M. Aeruginosins, protease inhibitors from the cyanobacterium Microcystis aeruginosa. Tetrahedron. 1999;55:10971–10988. doi: 10.1016/S0040-4020(99)00621-3. - DOI
1. Elkobi-Peer S., Faigenbaum R., Carmeli S. Bromine- and Chlorine-containing aeruginosins from Microcystis aeruginosa bloom material collected in Kibbutz Geva, Israel. J. Nat. Prod. 2012;75:2144–2151. doi: 10.1021/np3005612. - DOI - PubMed

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[1] Paerl H.W., Millie D.F. Physiological ecology of toxic aquatic cyanobacteria. Phycologiacal. 1996;35:160–167. doi: 10.2216/i0031-8884-35-6S-160.1. - DOI

[2] Paerl H.W., Millie D.F. Physiological ecology of toxic aquatic cyanobacteria. Phycologiacal. 1996;35:160–167. doi: 10.2216/i0031-8884-35-6S-160.1. - DOI

[3] Qin B., Li W., Zhu G., Wu T., Gao G. Cyanobacterial bloom management through integrated monitoring and forecasting in large shallow eutrophic Lake Taihu. J. Hazard. Mater. 2015;287:356–363. doi: 10.1016/j.jhazmat.2015年01月04日7. - DOI - PubMed

[4] Qin B., Li W., Zhu G., Wu T., Gao G. Cyanobacterial bloom management through integrated monitoring and forecasting in large shallow eutrophic Lake Taihu. J. Hazard. Mater. 2015;287:356–363. doi: 10.1016/j.jhazmat.2015年01月04日7. - DOI - PubMed

[5] Luesch H., Harrigan G.G., Goetz G., Horgen F.D. The Cyanobacterial origin of potent anticancer agents originally isolated from Sea Hares. Curr. Med. Chem. 2002;9:1791–1806. doi: 10.2174/0929867023369051. - DOI - PubMed

[6] Luesch H., Harrigan G.G., Goetz G., Horgen F.D. The Cyanobacterial origin of potent anticancer agents originally isolated from Sea Hares. Curr. Med. Chem. 2002;9:1791–1806. doi: 10.2174/0929867023369051. - DOI - PubMed

[7] Ishida K., Okita Y., Mastsuda H., Okino T., Murakami M. Aeruginosins, protease inhibitors from the cyanobacterium Microcystis aeruginosa. Tetrahedron. 1999;55:10971–10988. doi: 10.1016/S0040-4020(99)00621-3. - DOI

[8] Ishida K., Okita Y., Mastsuda H., Okino T., Murakami M. Aeruginosins, protease inhibitors from the cyanobacterium Microcystis aeruginosa. Tetrahedron. 1999;55:10971–10988. doi: 10.1016/S0040-4020(99)00621-3. - DOI

[9] Elkobi-Peer S., Faigenbaum R., Carmeli S. Bromine- and Chlorine-containing aeruginosins from Microcystis aeruginosa bloom material collected in Kibbutz Geva, Israel. J. Nat. Prod. 2012;75:2144–2151. doi: 10.1021/np3005612. - DOI - PubMed

[10] Elkobi-Peer S., Faigenbaum R., Carmeli S. Bromine- and Chlorine-containing aeruginosins from Microcystis aeruginosa bloom material collected in Kibbutz Geva, Israel. J. Nat. Prod. 2012;75:2144–2151. doi: 10.1021/np3005612. - DOI - PubMed

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Diversity, Biosynthesis and Bioactivity of Aeruginosins, a Family of Cyanobacteria-Derived Nonribosomal Linear Tetrapeptides

Affiliations

Diversity, Biosynthesis and Bioactivity of Aeruginosins, a Family of Cyanobacteria-Derived Nonribosomal Linear Tetrapeptides

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Research Materials