摘要
Staphylococcus aureus produces staphyloxanthin,a C30 carotenoid with golden color,as an antioxidant to promote bacterial resistance to reactive oxygen species.The biosynthesis pathway of staphyloxanthin involves a series of catalytic enzymes.Aldehyde dehydrogenase(AldH)is a dehydrogenase recently identified to convert 4,4’-diaponeurosporenaldehyde into 4,4’-diaponeurosporenoic acid during staphyloxanthin biosynthesis.Here,we present the crystallographic structures of apo-and holo-forms of S.aureus AldH.The dimeric enzyme contains a unique C-terminal helix,which resembles a“gatekeeper”helix found in human membrane-bound fatty aldehyde dehydrogenase(FALDH).Particularly,the helix adopts“open”and“closed”conformations in apo-and holo-AldH,respectively,to control the access of the substrate tunnel.Mutagenesis in combination with in vitro and in vivo activity assays identifies several residues essential for S.aureus AldH substrate recognition and enzyme catalytic turnover.Our results provide insights into substrate recognition of S.aureus AldH toward polyunsaturated long-chain aldehydes at atomic resolution.
基金
supported by the National Natural Science Foundation of China(21671203 and 21877131)
RGC of Hong Kong(17305415 and 17333616)
the Ministry of Education of China(IRT-17R111)
the Fundamental Research Funds for the Central Universities.