Exploration of marine natural resources in Indonesia and development of efficient strategies for the production of microbial halogenated metabolites

Abstract

Nature is a prolific source of organic products with diverse scaffolds and biological activities. The process of natural product discovery has gradually become more challenging, and advances in novel strategic approaches are essential to evolve natural product chemistry. Our focus has been on surveying untouched marine resources and fermentation to enhance microbial productive performance. The first topic is the screening of marine natural products isolated from Indonesian marine organisms for new types of bioactive compounds, such as antineoplastics, antimycobacterium substances, and inhibitors of protein tyrosine phosphatase 1B, sterol O-acyl-transferase, and bone morphogenetic protein-induced osteoblastic differentiation. The unique biological properties of marine organohalides are discussed herein and attempts to efficiently produce fungal halogenated metabolites are documented. This review presents an overview of our recent work accomplishments based on the MONOTORI study.

Keywords: Biological activities; Fungi; Indonesia; MONOTORI; Marine invertebrates; Organohalogens.

Fig. 1

a and b Rich natural environments in North Sulawesi; c coral reefs in the sea of North Sulawesi; d sampling of marine organisms by scuba diving (the diver in the picture is the author)

Fig. 2

Structures of lissoclibadin 1 (1) and papuamine (2) as anticancer compounds

Fig. 3

Structures of marine antimycobacterial substances 3–8

Fig. 4

Structures of marine protein tyrosine phosphatase inhibitors 9–21

Fig. 5

Structures of callyspongiamides A (22) and B (23) as SOAT inhibitors

Fig. 6

Structure of avarol (24) as a multifunctional inhibitor against PTP1B and SOAT1/2

Fig. 7

Structures of marine osteoblastogenesis inhibitors 25–30

Fig. 8

Structures of marine organohalogens 31–35 and related compound 36

Fig. 9

a Enhanced effects of agelasine G (33) and ageline B (36) on insulin-stimulated Akt phosphorylation levels in Huh-7 cells. b Effects of 33 and 36 on Akt phosphorylation levels in Huh-7 cells. p-Akt/t-Akt levels were shown as a ratio of that in the control group. Data are expressed as the mean ± SE (n = 4). ^#P < 0.05, ^##P < 0.01 vs the insulin treatment group

Fig. 10

Structures of 37–46 from a culture broth of the Palauan marine-derived fungus Trichoderma sp. TPU199

Fig. 11

Structure of 2-bromo-cladosporol D (47) from a culture broth of the Okinawan plant-associated fungus Cladosporium sp. TMPU1621