Developmental cycle and pharmaceutically relevant compounds of Salinispora actinobacteria isolated from Great Barrier Re

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APPLIED MICROBIAL AND CELL PHYSIOLOGY

Developmental cycle and pharmaceutically relevant compounds of Salinispora actinobacteria isolated from Great Barrier Reef marine sponges Yi Kai Ng & Amitha K. Hewavitharana & Richard Webb & P. Nicholas Shaw & John A. Fuerst

Received: 5 July 2012 / Revised: 16 September 2012 / Accepted: 29 September 2012 # Springer-Verlag Berlin Heidelberg 2012

Abstract The developmental cycle of the obligate marine antibiotic producer actinobacterium Salinispora arenicola isolated from a Great Barrier Reef marine sponge was investigated in relation to mycelium and spore ultrastructure, synthesis of rifamycin antibiotic compounds, and expression of genes correlated with spore formation and with rifamycin precursor synthesis. The developmental cycle of S. arenicola M413 on solid agar medium was characterized by substrate mycelium growth, change of colony color, and spore formation; spore formation occurred quite early in colony growth but development of black colonies occurred only at late stages, correlated with a change in spore maturity in relation to cell wall layers. Rifamycins were detected throughout the growth cycle, but changed in relative quantity at particular phases in the cycle, with a marked increase after 32 days. Expression of the spore division gene ssgA and the rifK gene for 3-amino-5-hydroxybenzoate synthase responsible for rifamycin precursor synthesis was seen even at early stages of the growth cycle. ssgA expression significantly increased between days 26 and 31, but rifK

Y. K. Ng : J. A. Fuerst (*) School of Chemistry and Molecular Bioscience, University of Queensland, Brisbane, Queensland 4072, Australia e-mail: [email protected] A. K. Hewavitharana : P. N. Shaw School of Pharmacy, University of Queensland, Brisbane, Queensland 4072, Australia R. Webb Centre for Microscopy and Microanalysis, University of Queensland, Brisbane, Queensland 4072, Australia

expression effectively remained constant throughout the growth cycle, consistent with the early synthesis of rifamycin. Factors other than precursor synthesis may be responsible for an observed late increase in rifamycin production. A useful approach for measuring and exploring the regulation of antibiotic synthesis and gene expression in the marine natural product producer S. arenicola has been established. Keywords Salinispora . Actinobacteria . Marine bacteria . Antibiotics . Electron microscopy . Developmental cycle

Introduction Almost half of the antibiotics discovered up to 2002 are derivatives of microbial natural products, making them the primary source from which new medicines are discovered (Berdy 2005). However, over the last few decades, efforts for drug discovery have shifted away from microbial products. This is partly due to a reduction in the ratio between the discovery of new chemical entities and identification of pharmacologically useful metabolites (Baltz 2005). The limited success of alternative discovery strategies, such as combinatorial chemistry, and the rise of multidrug-resistant pathogens