Lovastatin inAspergillus terreus: Fermented Rice Straw Extracts Interferes with Methane Production and Gene Expression inMethanobrevibacter smithii

Mohammad Faseleh Jahromi,Parisa Shokryazdan,Rosfarizan Mohamad,Juan Boo Liang,Yin Wan Ho,James Chin,Yong Meng Goh

doi:10.1155/2013/604721

Abstract

Lovastatin, a natural byproduct of some fungi, is able to inhibit HMG-CoA (3-hydroxy-3methyl glutaryl CoA) reductase. This is a key enzyme involved in isoprenoid synthesis and essential for cell membrane formation in methanogenic Archaea. In this paper, experiments were designed to test the hypothesis that lovastatin secreted by Aspergillus terreus in fermented rice straw extracts (FRSE) can inhibit growth and CH4 production in Methanobrevibacter smithii (a test methanogen). By HPLC analysis, 75% of the total lovastatin in FRSE was in the active hydroxyacid form, and in vitro studies confirmed that this had a stronger effect in reducing both growth and CH4 production in M. smithii compared to commercial lovastatin. Transmission electron micrographs revealed distorted morphological divisions of lovastatin- and FRSE-treated M. smithii cells, supporting its role in blocking normal cell membrane synthesis. Real-time PCR confirmed that both commercial lovastatin and FRSE increased (P < 0.01) the expression of HMG-CoA reductase gene (hmg). In addition, expressions of other gene transcripts in M. smithii. with a key involvement in methanogenesis were also affected. Experimental confirmation that CH4 production is inhibited by lovastatin in A. terreus-fermented rice straw paves the way for its evaluation as a feed additive for mitigating CH4 production in ruminants.

Highlights

The formation of isoprenoid chains is a key component of membrane phospholipid synthesis in Archaea
Lovastatin is an effective therapy in the treatment of hypercholesterolemia because of its ability to inhibit HMGCoA reductase activity, a key enzyme involved in cholesterol synthesis [16]
It is easy to ignore the fact that generic fungal statins have evolved to allow producer strains to gain a competitive survival advantage in complex ecological communities by interfering with the assembly of isoprenoid chains required for membrane phospholipid synthesis [17]

Summary

Introduction

The formation of isoprenoid chains is a key component of membrane phospholipid synthesis in Archaea. This pathway requires the production of mevalonic acid from 3-hydroxy3methyl glutaryl CoA catalyzed by the enzyme HMG-CoA reductase, a critical rate-limiting step shared in common with cholesterol biosynthesis in humans (Figure 1). The high cost of lovastatin preempts its use as a feed additive in the mitigation of ruminal CH4 production. Another approach that may be economically viable is to incorporate A. terreus as a feed supplement and inhibitor of methanogenic Archaea that produces methane in the process of methanogenesis (Figure 2).

C O C HO Phosphate

Materials and Methods

Results

Discussion