Adenosylhopane: the first intermediate in hopanoid side chain biosynthesis

Bradley, A. S.; Pearson, A.; Sáenz, J. P.; Marx, C. J. (2010) Organic Geochemistry, 41(10), 1075–1081. DOI: 10.1016/j.orggeochem.2010.07.003

Summary

This study identified adenosylhopane as the first intermediate in the biosynthesis of extended hopanoid side chains, using mutant strains of [[methylobacterium-extorquens|Methylobacterium extorquens]] AM1. Deletion of the gene hpnH (a radical SAM enzyme) eliminated all hopanoids longer than C31, while deletion of hpnG (a nucleoside phosphorylase) caused accumulation of adenosylhopane without further extended products. These results established a biosynthetic pathway in which S-adenosylmethionine donates its adenosyl moiety to the hopanoid ring system, followed by cleavage of adenine to yield downstream intermediates.

Key Findings

• The DhpnH mutant of M. extorquens produced only Diplopterol, diploptene, and methyldiplopterol (no C35 hopanoids)
• The DhpnG mutant accumulated adenosylhopane but no bacteriohopanetetrol or cyclitol ethers, placing adenosylhopane as the direct precursor to extended Bacteriohopanepolyols
• The proposed pathway involves addition of the adenosyl group from SAM by HpnH, followed by cleavage of adenine by HpnG, possibly yielding phosphoribohopane
• The diversity of extended hopanoids in nature likely reflects processes downstream of the adenosylhopane intermediate
• Some environmental adenosylhopane may result from diagenetic degradation of extended hopanoids rather than solely from biosynthetic accumulation

Our Contribution

Saenz contributed expertise in hopanoid lipid analysis by LC-MS, including comparison of retention times and mass spectra to reference organisms such as Rhodopseudomonas palustris and [[crocosphaera-watsonii|Crocosphaera watsonii]].

Significance

By identifying the first committed step in hopanoid side chain formation, this work provided a biochemical framework for understanding the diversity of Bacteriohopanepolyols in nature. The finding that adenosylhopane is a biosynthetic intermediate also refined its interpretation as a biomarker in environmental and geological samples, where it had previously been assumed to represent a terminal product of soil bacteria.