PMID- 36921345
OWN - NLM
STAT- MEDLINE
DCOM- 20230719
LR  - 20230719
IS  - 1554-8937 (Electronic)
IS  - 1554-8929 (Print)
IS  - 1554-8929 (Linking)
VI  - 18
IP  - 4
DP  - 2023 Apr 21
TI  - Unique Initiation and Termination Mechanisms Involved in the Biosynthesis of a 
      Hybrid Polyketide-Nonribosomal Peptide Lyngbyapeptin B Produced by the Marine 
      Cyanobacterium Moorena bouillonii.
PG  - 875-883
LID - 10.1021/acschembio.3c00011 [doi]
AB  - Lyngbyapeptin B is a hybrid polyketide-nonribosomal peptide isolated from 
      particular marine cyanobacteria. In this report, we carried out genome sequence 
      analysis of a producer cyanobacterium Moorena bouillonii to understand the 
      biosynthetic mechanisms that generate the unique structural features of 
      lyngbyapeptin B, including the (E)-3-methoxy-2-butenoyl starter unit and the 
      C-terminal thiazole moiety. We identified a putative lyngbyapeptin B biosynthetic 
      (lynB) gene cluster comprising nine open reading frames that include two 
      polyketide synthases (PKSs: LynB1 and LynB2), four nonribosomal peptide 
      synthetases (NRPSs: LynB3, LynB4, LynB5, and LynB6), a putative nonheme diiron 
      oxygenase (LynB7), a type II thioesterase (LynB8), and a hypothetical protein 
      (LynB9). In vitro enzymatic analysis of LynB2 with methyltransferase (MT) and 
      acyl carrier protein (ACP) domains revealed that the LynB2 MT domain (LynB2-MT) 
      catalyzes O-methylation of the acetoacetyl-LynB2 ACP domain (LynB2-ACP) to yield 
      (E)-3-methoxy-2-butenoyl-LynB2-ACP. In addition, in vitro enzymatic analysis of 
      LynB7 revealed that LynB7 catalyzes the oxidative decarboxylation of 
      (4R)-2-methyl-2-thiazoline-4-carboxylic acid to yield 2-methylthiazole in the 
      presence of Fe(2+) and molecular oxygen. This result indicates that LynB7 is 
      responsible for the last post-NRPS modification to give the C-terminal thiazole 
      moiety in lyngbyapeptin B biosynthesis. Overall, we identified and characterized 
      a new marine cyanobacterial hybrid PKS-NRPS biosynthetic gene cluster for 
      lyngbyapeptin B production, revealing two unique enzymatic logics.
FAU - Kudo, Fumitaka
AU  - Kudo F
AUID- ORCID: 0000-0002-4788-0063
AD  - Department of Chemistry, Tokyo Institute of Technology, 2-12-1 O-okayama, Tokyo 
      152-8551, Japan.
FAU - Chikuma, Takuji
AU  - Chikuma T
AD  - Department of Chemistry, Tokyo Institute of Technology, 2-12-1 O-okayama, Tokyo 
      152-8551, Japan.
FAU - Nambu, Mizuki
AU  - Nambu M
AD  - Department of Chemistry, Tokyo Institute of Technology, 2-12-1 O-okayama, Tokyo 
      152-8551, Japan.
FAU - Chisuga, Taichi
AU  - Chisuga T
AD  - Department of Chemistry, Tokyo Institute of Technology, 2-12-1 O-okayama, Tokyo 
      152-8551, Japan.
FAU - Sumimoto, Shimpei
AU  - Sumimoto S
AD  - Department of Chemistry, Faculty of Science and Technology, Keio University, 
      3-14-1 Hiyoshi, Kohoku-ku, Yokohama, Kanagawa 223-8522, Japan.
FAU - Iwasaki, Arihiro
AU  - Iwasaki A
AUID- ORCID: 0000-0002-3775-5066
AD  - Department of Chemistry, Faculty of Science and Technology, Keio University, 
      3-14-1 Hiyoshi, Kohoku-ku, Yokohama, Kanagawa 223-8522, Japan.
FAU - Suenaga, Kiyotake
AU  - Suenaga K
AUID- ORCID: 0000-0001-5343-5890
AD  - Department of Chemistry, Faculty of Science and Technology, Keio University, 
      3-14-1 Hiyoshi, Kohoku-ku, Yokohama, Kanagawa 223-8522, Japan.
FAU - Miyanaga, Akimasa
AU  - Miyanaga A
AUID- ORCID: 0000-0003-2219-6051
AD  - Department of Chemistry, Tokyo Institute of Technology, 2-12-1 O-okayama, Tokyo 
      152-8551, Japan.
FAU - Eguchi, Tadashi
AU  - Eguchi T
AUID- ORCID: 0000-0002-7830-7104
AD  - Department of Chemistry, Tokyo Institute of Technology, 2-12-1 O-okayama, Tokyo 
      152-8551, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230315
PL  - United States
TA  - ACS Chem Biol
JT  - ACS chemical biology
JID - 101282906
RN  - EC 6.3.2.- (Peptide Synthases)
RN  - 0 (Peptides)
RN  - 79956-01-7 (Polyketide Synthases)
RN  - 0 (Polyketides)
RN  - 0 (Thiazoles)
RN  - 0 (2-methylthiazole)
RN  - 0 (lyngbyapeptin B)
RN  - Moorea bouillonii
SB  - IM
MH  - *Cyanobacteria/chemistry/genetics/metabolism
MH  - Peptide Synthases/metabolism
MH  - *Peptides
MH  - Polyketide Synthases/metabolism
MH  - *Polyketides/chemistry
MH  - Thiazoles/metabolism
PMC - PMC10127204
COIS- The authors declare no competing financial interest.
EDAT- 2023/03/16 06:00
MHDA- 2023/04/24 06:41
PMCR- 2023/04/25
CRDT- 2023/03/15 18:42
PHST- 2023/04/24 06:41 [medline]
PHST- 2023/03/16 06:00 [pubmed]
PHST- 2023/03/15 18:42 [entrez]
PHST- 2023/04/25 00:00 [pmc-release]
AID - 10.1021/acschembio.3c00011 [doi]
PST - ppublish
SO  - ACS Chem Biol. 2023 Apr 21;18(4):875-883. doi: 10.1021/acschembio.3c00011. Epub 
      2023 Mar 15.