Elucidation of the B urkholderia cenocepacia hopanoid biosynthesis pathway uncovers functions for conserved proteins in hopanoid‐producing bacteria

• Published in: Environmental microbiology Vol. 17; no. 3; pp. 735 - 750
• Main Authors: Schmerk, Crystal L., Welander, Paula V., Hamad, Mohamad A., Bain, Katie L., Bernards, Mark A., Summons, Roger E., Valvano, Miguel A.
• Format: Journal Article
• Language: English
• Published: 01-03-2015
• ISSN: 1462-2912; 1462-2920
• DOI: 10.1111/1462-2920.12509

Hopanoids are bacterial surrogates of eukaryotic membrane sterols and among earth's most abundant natural products. Their molecular fossils remain in sediments spanning more than a billion years. However, hopanoid metabolism and function are not fully understood.
B
urkholderia
species are environmental opportunistic pathogens that produce hopanoids and also occupy diverse ecological niches. We investigated hopanoids biosynthesis in
B
urkholderia cenocepacia
by deletion mutagenesis and structural characterization of the hopanoids produced by the mutants. The enzymes encoded by
hpnH
and
hpnG
were essential for production of all
C
35
extended hopanoids, including bacteriohopanetetrol (
BHT
),
BHT
glucosamine and
BHT
cyclitol ether. Deletion of
hpnI
resulted in
BHT
production, while Δ
hpnJ
produced only
BHT
glucosamine. Thus,
HpnI
is required for
BHT
glucosamine production while
HpnJ
is responsible for its conversion to the cyclitol ether. The Δ
hpnH
and Δ
hpnG
mutants could not grow under any stress condition tested, whereas Δ
hpnI
, Δ
hpnJ
and Δ
hpnK
displayed wild‐type growth rates when exposed to detergent, but varying levels of sensitivity to low
pH
and polymyxin
B
. This study not only elucidates the biosynthetic pathway of hopanoids in
B
. cenocepacia
, but also uncovers a biosynthetic role for the conserved proteins
HpnI
,
HpnJ
and
HpnK
in other hopanoid‐producing bacteria.