The Role of a Nonribosomal Peptide Synthetase in L-Lysine Lactamization During Capuramycin Biosynthesis
메타 데이터
바이오화학분류
바이오플라스틱
기타
바이오정밀화학
기타
화장품용 기능성소재
기타
의료용 화학소재
식품첨가제
논문
The Role of a Nonribosomal Peptide Synthetase in L-Lysine Lactamization During Capuramycin Biosynthesis
학술지
Chembiochem : a European journal of chemical biology
저자명
Liu, Xiaodong; Jin, Yuanyuan; Cui, Zheng; Nonaka, Koichi; Baba, Satoshi; Funabashi, Masanori; Yang, Zhaoyong; Van Lanen, Steven G.
초록
<P><B>Abstract</B></P><P>Capuramycins are one of several known classes of natural products that contain an <SMALL>l</SMALL>‐Lys‐derived <SMALL>l</SMALL>‐α‐amino‐ɛ‐caprolactam (<SMALL>l</SMALL>‐ACL) unit. The α‐amino group of <SMALL>l</SMALL>‐ACL in a capuramycin is linked to an unsaturated hexuronic acid component through an amide bond that was previously shown to originate by an ATP‐independent enzymatic route. With the aid of a combined in vivo and in vitro approach, a predicted tridomain nonribosomal peptide synthetase CapU is functionally characterized here as the ATP‐dependent amide‐bond‐forming catalyst responsible for the biosynthesis of the remaining amide bond present in <SMALL>l</SMALL>‐ACL. The results are consistent with the adenylation domain of CapU as the essential catalytic component for <SMALL>l</SMALL>‐Lys activation and thioesterification of the adjacent thiolation domain. However, in contrast to expectations, lactamization does not require any additional domains or proteins and is likely a nonenzymatic event. The results set the stage for examining whether a similar NRPS‐mediated mechanism is employed in the biosynthesis of other <SMALL>l</SMALL>‐ACL‐containing natural products and, just as intriguingly, how spontaneous lactamization is avoided in the numerous NRPS‐derived peptides that contain an unmodified <SMALL>l</SMALL>‐Lys residue.</P>